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Variability in micro RNA (miRNA) abundance, speciation and complexity amongst different human populations and potential relevance to Alzheimer's disease (AD).

Lukiw WJ - Front Cell Neurosci (2013)

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Neuroscience and Ophthalmology, LSU Neuroscience Center, Louisiana State University Health Sciences Center New Orleans, LA, USA.

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Toward the end of his 1976 book entitled “Vitamin C and the Common Cold” Linus Pauling included an interesting chapter on “human biochemical individuality” that defined some important parameters on individual human genotypic versus phenotypic variation, based in part on studies from hemoglobin genetics (Pauling, )... If we assume that there are about 26,600 human genes available to be expressed in each cell and that each gene is responsible for at least one inherited trait or genetic function (a number that is probably vastly underestimated), in a global human population exceeding 7 billion it then becomes exceedingly difficult to define “human genetic normalcy. ” These ideas form the basis for the evolving concept of “human genetic individuality” and our ongoing efforts to better understand the genotypic basis of human phenotypic diversity in both health and disease (Li et al., ; Raj et al., ; Lukiw, ,; Olson, ; this paper)... These studies have been very valuable since the profiling of mRNA and/or miRNA can provide a powerful “snapshot” into the physiological status of a human cell or tissue in health and disease, and may even be predictive for the prognosis and/or diagnosis for the future outcomes of other AD patients... Steady-state mRNA and miRNA levels from different individuals clearly indicates that the abundance and speciation of these RNAs within clearly defined anatomical regions can significantly differ between samples analyzed, suggesting that genetic variation and extraneous effects, including age, gender, body mass index (BMI), apolipoprotein E (ApoE), beta-amyloid cleavage enzyme (BACE) and other AD-relevant allele status, life-style and intrinsic population effects can influence the profile of mRNA or miRNA abundance and complexity (Colangelo et al., ; Cui et al., ; Lukiw, ; Lukiw and Pogue, ; Williams et al., ; Sethi and Lukiw, ; Ginsberg et al., )... These patterns are further complicated by tissue acquisition and quality control parameters that include agonal effects, the analytical approach, and the death-to-brain freezing interval for post-mortem human tissues (McLachlan et al., ; Cui et al., ; Williams et al., ; Sethi and Lukiw, )... Agonal effects include the circumstances accompanying brain death, such as whether or not fever (i.e., heat shock) was present, whether there was interceding or accompanying illness including, commonly, pneumonia or cerebrovascular disease, and other pathophsyiological or interrelated procedural or clinical factors (Sethi and Lukiw, ; Raj et al., ; Hulse and Cai, )... To illustrate one important example is the miRNA abundance and speciation of a small family of inducible, NF-kB-sensitive miRNAs in two different American populations—Caucasian Americans and African Americans afflicted with AD (Figure 1)... Interestingly, when comparing AD in human populations, African Americans and Hispanics appear to have an increased frequency and severity of AD when compared to Caucasians, which may be independent of their APOE genotype (Tang et al., ; Shadlen et al., ; Reitz et al., )... The current results further suggest that in contrast to a recent mRNA-based study of genetic homogeneity in aging humans (Colantuoni et al., ), increased abundance of pathological miRNAs in progressive neurodegenerative disorders may reflect gene expression patterns highly characteristic of the AD process in certain human populations... These results further underscore basic differences in miRNA versus mRNA function, in accordance with their differential modes of generation, processing and signaling in development, aging and disease... Large rigorous population-based studies involving these multiple risk parameters still need to be compiled, researched and analyzed (Williams et al., ; Nussbaum, )... Lastly, much independently derived data comparable to that shown in Figure 1 supports the idea that the genetics and epigenetics of AD varies widely amongst different human populations with different genetic backgrounds, and these observations are in accordance with the concept of “human genetic individuality. ” If molecular-genetic and epigenetic profiles of AD brain samples are any indication of AD phenotypic variation then there may be real and significant inter-ethnic differences in AD epidemiology, incidence, disease course and progression.

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Related in: MedlinePlus

Incidence of miRNA abundance, speciation and complexity for 5 NF-kB-sensitive pro-inflammatory miRNAs in the superior temporal lobe (Brodmann Area A22) of 2 different human populations: The current explosion in miRNA profiling of human disease, including neuro-degenerative diseases such as Alzheimer's disease (AD), underscores “human genetic individuality.” Preliminary data suggests that there is considerable variation in miRNA abundance, speciation and complexity in human populations, and variation in miRNA abundance amongst individuals or populations may be a reflection of their individual genetic-based susceptibility to disease incidence or severity. (A) depicts a representative color-coded cluster diagram for 2 control and 2 selected “AD” populations; control-1 miRNA signals are derived from Caucasian Americans [age mean ± 1 standard deviation (SD) = 75.5 ± 8.4 year] and control-2 miRNA signals (age mean ± 1 SD = 76.1 ± 7.8 year) are derived from African Americans; similarly AD-1 miRNA signals are derived from Caucasian Americans [age mean ± 1 SD = 77.4 ± 7.5 year] with AD, and AD-2 miRNA signals are derived from African Americans (age mean ± 1 SD = 76.6 ± 8.2 year) with AD; all AD cases were for moderate-to-advanced stages of AD. Because, as single stranded ribonucleotides, miRNAs appear to have a relatively short half-life, all PMIs had a mean of 2.1 h or less (Sethi and Lukiw, 2009; Cui et al., 2010); there were no significant differences in age, PMI, ApoE allele status, RNA quality (all RIN values were 8.1–9.0) or yield between the control or AD groups (p > 0.05, ANOVA), or between the Caucasian and African American groups; note the higher general expression for miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155 (a) for all AD cases over controls and (b) for AD-2 versus AD-1; miRNAs in all AD cases were compared to 2 unchanging internal controls miRNA-183 and 5S RNA in the same brain sample; the numbers “1,” “2” and “3” are from individual control or AD cases; the letter “P” (also analyzed in B); using miRNA arrays, in Caucasian Americans miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155 were found to be up-regulated an average of 1.5-to-3.5 fold over age-matched controls, in African Americans this same group of miRNAs averaged an up-regulation of 3-to-5-fold over age-matched controls. (B) (bar graph) depicts quantitative results using RT-PCR, comparing AD-1 miRNA abundance [AD, (N = 8) relative to control miRNA (N = 8) signals; Caucasian Americans, set to 1.0 (for ease of comparison; dashed horizontal line)] to AD-2 miRNA abundance [AD (N = 8) relative to control miRNA (N = 8) signals; African Americans]; the data is suggestive of significantly higher miRNA abundance for these 5 potentially pathogenic miRNAs in the AD-2 group which may, in part, form a molecular-genetic basis for the predisposition of African Americans, and perhaps other ethnic groups, to different incidences of AD-type neuropathology, including variations in dementia development, severity, age of onset, progression, course and epidemiology (Espino and Lewis, 1998; Tang et al., 1998; Shadlen et al., 1999; Cui et al., 2010; Venketasubramanian et al., 2010; Reitz et al., 2013; this paper); *p < 0.01; **p < 0.05 (ANOVA). As further discussed in the text, selective differences in miRNA abundance may be useful in AD diagnosis and individualistic therapeutic strategies, to tailor more effective clinical treatment for AD and other progressive, age-related neurological disorders of the human CNS.
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Figure 1: Incidence of miRNA abundance, speciation and complexity for 5 NF-kB-sensitive pro-inflammatory miRNAs in the superior temporal lobe (Brodmann Area A22) of 2 different human populations: The current explosion in miRNA profiling of human disease, including neuro-degenerative diseases such as Alzheimer's disease (AD), underscores “human genetic individuality.” Preliminary data suggests that there is considerable variation in miRNA abundance, speciation and complexity in human populations, and variation in miRNA abundance amongst individuals or populations may be a reflection of their individual genetic-based susceptibility to disease incidence or severity. (A) depicts a representative color-coded cluster diagram for 2 control and 2 selected “AD” populations; control-1 miRNA signals are derived from Caucasian Americans [age mean ± 1 standard deviation (SD) = 75.5 ± 8.4 year] and control-2 miRNA signals (age mean ± 1 SD = 76.1 ± 7.8 year) are derived from African Americans; similarly AD-1 miRNA signals are derived from Caucasian Americans [age mean ± 1 SD = 77.4 ± 7.5 year] with AD, and AD-2 miRNA signals are derived from African Americans (age mean ± 1 SD = 76.6 ± 8.2 year) with AD; all AD cases were for moderate-to-advanced stages of AD. Because, as single stranded ribonucleotides, miRNAs appear to have a relatively short half-life, all PMIs had a mean of 2.1 h or less (Sethi and Lukiw, 2009; Cui et al., 2010); there were no significant differences in age, PMI, ApoE allele status, RNA quality (all RIN values were 8.1–9.0) or yield between the control or AD groups (p > 0.05, ANOVA), or between the Caucasian and African American groups; note the higher general expression for miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155 (a) for all AD cases over controls and (b) for AD-2 versus AD-1; miRNAs in all AD cases were compared to 2 unchanging internal controls miRNA-183 and 5S RNA in the same brain sample; the numbers “1,” “2” and “3” are from individual control or AD cases; the letter “P” (also analyzed in B); using miRNA arrays, in Caucasian Americans miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155 were found to be up-regulated an average of 1.5-to-3.5 fold over age-matched controls, in African Americans this same group of miRNAs averaged an up-regulation of 3-to-5-fold over age-matched controls. (B) (bar graph) depicts quantitative results using RT-PCR, comparing AD-1 miRNA abundance [AD, (N = 8) relative to control miRNA (N = 8) signals; Caucasian Americans, set to 1.0 (for ease of comparison; dashed horizontal line)] to AD-2 miRNA abundance [AD (N = 8) relative to control miRNA (N = 8) signals; African Americans]; the data is suggestive of significantly higher miRNA abundance for these 5 potentially pathogenic miRNAs in the AD-2 group which may, in part, form a molecular-genetic basis for the predisposition of African Americans, and perhaps other ethnic groups, to different incidences of AD-type neuropathology, including variations in dementia development, severity, age of onset, progression, course and epidemiology (Espino and Lewis, 1998; Tang et al., 1998; Shadlen et al., 1999; Cui et al., 2010; Venketasubramanian et al., 2010; Reitz et al., 2013; this paper); *p < 0.01; **p < 0.05 (ANOVA). As further discussed in the text, selective differences in miRNA abundance may be useful in AD diagnosis and individualistic therapeutic strategies, to tailor more effective clinical treatment for AD and other progressive, age-related neurological disorders of the human CNS.

Mentions: To illustrate one important example is the miRNA abundance and speciation of a small family of inducible, NF-kB-sensitive miRNAs in two different American populations—Caucasian Americans and African Americans afflicted with AD (Figure 1). A pathogenic quintet of up-regulated miRNAs have been described and partially characterized, and these include miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155, which have been shown to be involved in chronic inflammatory degeneration by many independent groups in multiple human diseases with a progressive inflammatory and degenerative component (Lukiw, 2007; Williams et al., 2007; Wang et al., 2009; Culpan et al., 2011; Lukiw et al., 2011; Hu et al., 2012; Iyer et al., 2012; Saba et al., 2012; Lukiw, 2013; Nussbaum, 2013; Zhao et al., 2013). In AD these five up-regulated miRNAs appear to play important roles in the down-regulation of brain gene expression normally involved in the brain's neurotrophic support, synaptogenesis, the innate-immune response, NF-kB-mediated inflammatory signaling and amyloidogenesis (Cui et al., 2005; Sethi and Lukiw, 2009; Lukiw, 2012a,b; Zhao et al., 2013). Preliminary data indicates that greater general abundance in the expression of these five miRNAs may in part explain differences in the incidence, course and/or severity of AD amongst elderly Caucasian American, African American, Hispanics and other minority populations. Interestingly, when comparing AD in human populations, African Americans and Hispanics appear to have an increased frequency and severity of AD when compared to Caucasians, which may be independent of their APOE genotype (Tang et al., 1998; Shadlen et al., 1999; Reitz et al., 2013). The current results further suggest that in contrast to a recent mRNA-based study of genetic homogeneity in aging humans (Colantuoni et al., 2011), increased abundance of pathological miRNAs in progressive neurodegenerative disorders may reflect gene expression patterns highly characteristic of the AD process in certain human populations. These results further underscore basic differences in miRNA versus mRNA function, in accordance with their differential modes of generation, processing and signaling in development, aging and disease. As both mRNA and miRNA are intrinsically unstable molecules with short half-lives, differential studies using only high quality, high RIN value, short post-mortem interval (PMI) mRNA and miRNA may be very useful in furthering our understanding of AD epidemiology, and ultimately also be of use diagnostically and therapeutically in the clinical management of this common neurological disorder (Espino and Lewis, 1998; Froehlich et al., 2001; Cowley et al., 2009; Sethi and Lukiw, 2009; Venketasubramanian et al., 2010; Lukiw, 2013; Reitz et al., 2013).


Variability in micro RNA (miRNA) abundance, speciation and complexity amongst different human populations and potential relevance to Alzheimer's disease (AD).

Lukiw WJ - Front Cell Neurosci (2013)

Incidence of miRNA abundance, speciation and complexity for 5 NF-kB-sensitive pro-inflammatory miRNAs in the superior temporal lobe (Brodmann Area A22) of 2 different human populations: The current explosion in miRNA profiling of human disease, including neuro-degenerative diseases such as Alzheimer's disease (AD), underscores “human genetic individuality.” Preliminary data suggests that there is considerable variation in miRNA abundance, speciation and complexity in human populations, and variation in miRNA abundance amongst individuals or populations may be a reflection of their individual genetic-based susceptibility to disease incidence or severity. (A) depicts a representative color-coded cluster diagram for 2 control and 2 selected “AD” populations; control-1 miRNA signals are derived from Caucasian Americans [age mean ± 1 standard deviation (SD) = 75.5 ± 8.4 year] and control-2 miRNA signals (age mean ± 1 SD = 76.1 ± 7.8 year) are derived from African Americans; similarly AD-1 miRNA signals are derived from Caucasian Americans [age mean ± 1 SD = 77.4 ± 7.5 year] with AD, and AD-2 miRNA signals are derived from African Americans (age mean ± 1 SD = 76.6 ± 8.2 year) with AD; all AD cases were for moderate-to-advanced stages of AD. Because, as single stranded ribonucleotides, miRNAs appear to have a relatively short half-life, all PMIs had a mean of 2.1 h or less (Sethi and Lukiw, 2009; Cui et al., 2010); there were no significant differences in age, PMI, ApoE allele status, RNA quality (all RIN values were 8.1–9.0) or yield between the control or AD groups (p > 0.05, ANOVA), or between the Caucasian and African American groups; note the higher general expression for miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155 (a) for all AD cases over controls and (b) for AD-2 versus AD-1; miRNAs in all AD cases were compared to 2 unchanging internal controls miRNA-183 and 5S RNA in the same brain sample; the numbers “1,” “2” and “3” are from individual control or AD cases; the letter “P” (also analyzed in B); using miRNA arrays, in Caucasian Americans miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155 were found to be up-regulated an average of 1.5-to-3.5 fold over age-matched controls, in African Americans this same group of miRNAs averaged an up-regulation of 3-to-5-fold over age-matched controls. (B) (bar graph) depicts quantitative results using RT-PCR, comparing AD-1 miRNA abundance [AD, (N = 8) relative to control miRNA (N = 8) signals; Caucasian Americans, set to 1.0 (for ease of comparison; dashed horizontal line)] to AD-2 miRNA abundance [AD (N = 8) relative to control miRNA (N = 8) signals; African Americans]; the data is suggestive of significantly higher miRNA abundance for these 5 potentially pathogenic miRNAs in the AD-2 group which may, in part, form a molecular-genetic basis for the predisposition of African Americans, and perhaps other ethnic groups, to different incidences of AD-type neuropathology, including variations in dementia development, severity, age of onset, progression, course and epidemiology (Espino and Lewis, 1998; Tang et al., 1998; Shadlen et al., 1999; Cui et al., 2010; Venketasubramanian et al., 2010; Reitz et al., 2013; this paper); *p < 0.01; **p < 0.05 (ANOVA). As further discussed in the text, selective differences in miRNA abundance may be useful in AD diagnosis and individualistic therapeutic strategies, to tailor more effective clinical treatment for AD and other progressive, age-related neurological disorders of the human CNS.
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Related In: Results  -  Collection

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Figure 1: Incidence of miRNA abundance, speciation and complexity for 5 NF-kB-sensitive pro-inflammatory miRNAs in the superior temporal lobe (Brodmann Area A22) of 2 different human populations: The current explosion in miRNA profiling of human disease, including neuro-degenerative diseases such as Alzheimer's disease (AD), underscores “human genetic individuality.” Preliminary data suggests that there is considerable variation in miRNA abundance, speciation and complexity in human populations, and variation in miRNA abundance amongst individuals or populations may be a reflection of their individual genetic-based susceptibility to disease incidence or severity. (A) depicts a representative color-coded cluster diagram for 2 control and 2 selected “AD” populations; control-1 miRNA signals are derived from Caucasian Americans [age mean ± 1 standard deviation (SD) = 75.5 ± 8.4 year] and control-2 miRNA signals (age mean ± 1 SD = 76.1 ± 7.8 year) are derived from African Americans; similarly AD-1 miRNA signals are derived from Caucasian Americans [age mean ± 1 SD = 77.4 ± 7.5 year] with AD, and AD-2 miRNA signals are derived from African Americans (age mean ± 1 SD = 76.6 ± 8.2 year) with AD; all AD cases were for moderate-to-advanced stages of AD. Because, as single stranded ribonucleotides, miRNAs appear to have a relatively short half-life, all PMIs had a mean of 2.1 h or less (Sethi and Lukiw, 2009; Cui et al., 2010); there were no significant differences in age, PMI, ApoE allele status, RNA quality (all RIN values were 8.1–9.0) or yield between the control or AD groups (p > 0.05, ANOVA), or between the Caucasian and African American groups; note the higher general expression for miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155 (a) for all AD cases over controls and (b) for AD-2 versus AD-1; miRNAs in all AD cases were compared to 2 unchanging internal controls miRNA-183 and 5S RNA in the same brain sample; the numbers “1,” “2” and “3” are from individual control or AD cases; the letter “P” (also analyzed in B); using miRNA arrays, in Caucasian Americans miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155 were found to be up-regulated an average of 1.5-to-3.5 fold over age-matched controls, in African Americans this same group of miRNAs averaged an up-regulation of 3-to-5-fold over age-matched controls. (B) (bar graph) depicts quantitative results using RT-PCR, comparing AD-1 miRNA abundance [AD, (N = 8) relative to control miRNA (N = 8) signals; Caucasian Americans, set to 1.0 (for ease of comparison; dashed horizontal line)] to AD-2 miRNA abundance [AD (N = 8) relative to control miRNA (N = 8) signals; African Americans]; the data is suggestive of significantly higher miRNA abundance for these 5 potentially pathogenic miRNAs in the AD-2 group which may, in part, form a molecular-genetic basis for the predisposition of African Americans, and perhaps other ethnic groups, to different incidences of AD-type neuropathology, including variations in dementia development, severity, age of onset, progression, course and epidemiology (Espino and Lewis, 1998; Tang et al., 1998; Shadlen et al., 1999; Cui et al., 2010; Venketasubramanian et al., 2010; Reitz et al., 2013; this paper); *p < 0.01; **p < 0.05 (ANOVA). As further discussed in the text, selective differences in miRNA abundance may be useful in AD diagnosis and individualistic therapeutic strategies, to tailor more effective clinical treatment for AD and other progressive, age-related neurological disorders of the human CNS.
Mentions: To illustrate one important example is the miRNA abundance and speciation of a small family of inducible, NF-kB-sensitive miRNAs in two different American populations—Caucasian Americans and African Americans afflicted with AD (Figure 1). A pathogenic quintet of up-regulated miRNAs have been described and partially characterized, and these include miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155, which have been shown to be involved in chronic inflammatory degeneration by many independent groups in multiple human diseases with a progressive inflammatory and degenerative component (Lukiw, 2007; Williams et al., 2007; Wang et al., 2009; Culpan et al., 2011; Lukiw et al., 2011; Hu et al., 2012; Iyer et al., 2012; Saba et al., 2012; Lukiw, 2013; Nussbaum, 2013; Zhao et al., 2013). In AD these five up-regulated miRNAs appear to play important roles in the down-regulation of brain gene expression normally involved in the brain's neurotrophic support, synaptogenesis, the innate-immune response, NF-kB-mediated inflammatory signaling and amyloidogenesis (Cui et al., 2005; Sethi and Lukiw, 2009; Lukiw, 2012a,b; Zhao et al., 2013). Preliminary data indicates that greater general abundance in the expression of these five miRNAs may in part explain differences in the incidence, course and/or severity of AD amongst elderly Caucasian American, African American, Hispanics and other minority populations. Interestingly, when comparing AD in human populations, African Americans and Hispanics appear to have an increased frequency and severity of AD when compared to Caucasians, which may be independent of their APOE genotype (Tang et al., 1998; Shadlen et al., 1999; Reitz et al., 2013). The current results further suggest that in contrast to a recent mRNA-based study of genetic homogeneity in aging humans (Colantuoni et al., 2011), increased abundance of pathological miRNAs in progressive neurodegenerative disorders may reflect gene expression patterns highly characteristic of the AD process in certain human populations. These results further underscore basic differences in miRNA versus mRNA function, in accordance with their differential modes of generation, processing and signaling in development, aging and disease. As both mRNA and miRNA are intrinsically unstable molecules with short half-lives, differential studies using only high quality, high RIN value, short post-mortem interval (PMI) mRNA and miRNA may be very useful in furthering our understanding of AD epidemiology, and ultimately also be of use diagnostically and therapeutically in the clinical management of this common neurological disorder (Espino and Lewis, 1998; Froehlich et al., 2001; Cowley et al., 2009; Sethi and Lukiw, 2009; Venketasubramanian et al., 2010; Lukiw, 2013; Reitz et al., 2013).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Neuroscience and Ophthalmology, LSU Neuroscience Center, Louisiana State University Health Sciences Center New Orleans, LA, USA.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Toward the end of his 1976 book entitled “Vitamin C and the Common Cold” Linus Pauling included an interesting chapter on “human biochemical individuality” that defined some important parameters on individual human genotypic versus phenotypic variation, based in part on studies from hemoglobin genetics (Pauling, )... If we assume that there are about 26,600 human genes available to be expressed in each cell and that each gene is responsible for at least one inherited trait or genetic function (a number that is probably vastly underestimated), in a global human population exceeding 7 billion it then becomes exceedingly difficult to define “human genetic normalcy. ” These ideas form the basis for the evolving concept of “human genetic individuality” and our ongoing efforts to better understand the genotypic basis of human phenotypic diversity in both health and disease (Li et al., ; Raj et al., ; Lukiw, ,; Olson, ; this paper)... These studies have been very valuable since the profiling of mRNA and/or miRNA can provide a powerful “snapshot” into the physiological status of a human cell or tissue in health and disease, and may even be predictive for the prognosis and/or diagnosis for the future outcomes of other AD patients... Steady-state mRNA and miRNA levels from different individuals clearly indicates that the abundance and speciation of these RNAs within clearly defined anatomical regions can significantly differ between samples analyzed, suggesting that genetic variation and extraneous effects, including age, gender, body mass index (BMI), apolipoprotein E (ApoE), beta-amyloid cleavage enzyme (BACE) and other AD-relevant allele status, life-style and intrinsic population effects can influence the profile of mRNA or miRNA abundance and complexity (Colangelo et al., ; Cui et al., ; Lukiw, ; Lukiw and Pogue, ; Williams et al., ; Sethi and Lukiw, ; Ginsberg et al., )... These patterns are further complicated by tissue acquisition and quality control parameters that include agonal effects, the analytical approach, and the death-to-brain freezing interval for post-mortem human tissues (McLachlan et al., ; Cui et al., ; Williams et al., ; Sethi and Lukiw, )... Agonal effects include the circumstances accompanying brain death, such as whether or not fever (i.e., heat shock) was present, whether there was interceding or accompanying illness including, commonly, pneumonia or cerebrovascular disease, and other pathophsyiological or interrelated procedural or clinical factors (Sethi and Lukiw, ; Raj et al., ; Hulse and Cai, )... To illustrate one important example is the miRNA abundance and speciation of a small family of inducible, NF-kB-sensitive miRNAs in two different American populations—Caucasian Americans and African Americans afflicted with AD (Figure 1)... Interestingly, when comparing AD in human populations, African Americans and Hispanics appear to have an increased frequency and severity of AD when compared to Caucasians, which may be independent of their APOE genotype (Tang et al., ; Shadlen et al., ; Reitz et al., )... The current results further suggest that in contrast to a recent mRNA-based study of genetic homogeneity in aging humans (Colantuoni et al., ), increased abundance of pathological miRNAs in progressive neurodegenerative disorders may reflect gene expression patterns highly characteristic of the AD process in certain human populations... These results further underscore basic differences in miRNA versus mRNA function, in accordance with their differential modes of generation, processing and signaling in development, aging and disease... Large rigorous population-based studies involving these multiple risk parameters still need to be compiled, researched and analyzed (Williams et al., ; Nussbaum, )... Lastly, much independently derived data comparable to that shown in Figure 1 supports the idea that the genetics and epigenetics of AD varies widely amongst different human populations with different genetic backgrounds, and these observations are in accordance with the concept of “human genetic individuality. ” If molecular-genetic and epigenetic profiles of AD brain samples are any indication of AD phenotypic variation then there may be real and significant inter-ethnic differences in AD epidemiology, incidence, disease course and progression.

No MeSH data available.


Related in: MedlinePlus