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Early neurone loss in Alzheimer's disease: cortical or subcortical?

Arendt T, Brückner MK, Morawski M, Jäger C, Gertz HJ - Acta Neuropathol Commun (2015)

Bottom Line: In all three areas, neurone loss becomes detectable already at preclinical stages and is clearly manifest at prodromal AD/MCI.At more advanced AD, cell loss is most pronounced in the NbM > LC > layer-II EC.During early AD, however, the extent of cell loss is fairly balanced between all three areas without clear indications for a preference of one area.

View Article: PubMed Central - PubMed

ABSTRACT
Alzheimer's disease (AD) is a degenerative disorder where the distribution of pathology throughout the brain is not random but follows a predictive pattern used for pathological staging. While the involvement of defined functional systems is fairly well established for more advanced stages, the initial sites of degeneration are still ill defined. The prevailing concept suggests an origin within the transentorhinal and entorhinal cortex (EC) from where pathology spreads to other areas. Still, this concept has been challenged recently suggesting a potential origin of degeneration in nonthalamic subcortical nuclei giving rise to cortical innervation such as locus coeruleus (LC) and nucleus basalis of Meynert (NbM). To contribute to the identification of the early site of degeneration, here, we address the question whether cortical or subcortical degeneration occurs more early and develops more quickly during progression of AD. To this end, we stereologically assessed neurone counts in the NbM, LC and EC layer-II in the same AD patients ranging from preclinical stages to severe dementia. In all three areas, neurone loss becomes detectable already at preclinical stages and is clearly manifest at prodromal AD/MCI. At more advanced AD, cell loss is most pronounced in the NbM > LC > layer-II EC. During early AD, however, the extent of cell loss is fairly balanced between all three areas without clear indications for a preference of one area. We can thus not rule out that there is more than one way of spreading from its site of origin or that degeneration even occurs independently at several sites in parallel.

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Comparison of effect sizedfor neurone loss in the nucleus basalis of Meynert, locus coeruleus and entorhinal cortex layer II.
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Fig2: Comparison of effect sizedfor neurone loss in the nucleus basalis of Meynert, locus coeruleus and entorhinal cortex layer II.

Mentions: To make the effects of AD on neurone number comparable between the different regions, we calculated the effect size “d” of cell loss compared to the appropriate control group (Figure 2). At preclinical AD, effect size matched the criteria for a “small effect” (defined as 0.2 < d < 0.3) [79,80]. It was somewhat larger in the NbM (NbM: d = 0.32), compared to LC and entorhinal cortex, layer II (LC: d = 0.22; entorhinal cortex, layer II: d = 0.25). At prodromal AD/MCI, effect size matched the criteria of a “large effect” (defined as d > 0.8) [79,80]. At this stage of the disease, it was basically indistinguishable between the three areas (NbM: d = 0.95; LC: d = 0.98; entorhinal cortex, layer II: d = 1.06).Figure 2


Early neurone loss in Alzheimer's disease: cortical or subcortical?

Arendt T, Brückner MK, Morawski M, Jäger C, Gertz HJ - Acta Neuropathol Commun (2015)

Comparison of effect sizedfor neurone loss in the nucleus basalis of Meynert, locus coeruleus and entorhinal cortex layer II.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359478&req=5

Fig2: Comparison of effect sizedfor neurone loss in the nucleus basalis of Meynert, locus coeruleus and entorhinal cortex layer II.
Mentions: To make the effects of AD on neurone number comparable between the different regions, we calculated the effect size “d” of cell loss compared to the appropriate control group (Figure 2). At preclinical AD, effect size matched the criteria for a “small effect” (defined as 0.2 < d < 0.3) [79,80]. It was somewhat larger in the NbM (NbM: d = 0.32), compared to LC and entorhinal cortex, layer II (LC: d = 0.22; entorhinal cortex, layer II: d = 0.25). At prodromal AD/MCI, effect size matched the criteria of a “large effect” (defined as d > 0.8) [79,80]. At this stage of the disease, it was basically indistinguishable between the three areas (NbM: d = 0.95; LC: d = 0.98; entorhinal cortex, layer II: d = 1.06).Figure 2

Bottom Line: In all three areas, neurone loss becomes detectable already at preclinical stages and is clearly manifest at prodromal AD/MCI.At more advanced AD, cell loss is most pronounced in the NbM > LC > layer-II EC.During early AD, however, the extent of cell loss is fairly balanced between all three areas without clear indications for a preference of one area.

View Article: PubMed Central - PubMed

ABSTRACT
Alzheimer's disease (AD) is a degenerative disorder where the distribution of pathology throughout the brain is not random but follows a predictive pattern used for pathological staging. While the involvement of defined functional systems is fairly well established for more advanced stages, the initial sites of degeneration are still ill defined. The prevailing concept suggests an origin within the transentorhinal and entorhinal cortex (EC) from where pathology spreads to other areas. Still, this concept has been challenged recently suggesting a potential origin of degeneration in nonthalamic subcortical nuclei giving rise to cortical innervation such as locus coeruleus (LC) and nucleus basalis of Meynert (NbM). To contribute to the identification of the early site of degeneration, here, we address the question whether cortical or subcortical degeneration occurs more early and develops more quickly during progression of AD. To this end, we stereologically assessed neurone counts in the NbM, LC and EC layer-II in the same AD patients ranging from preclinical stages to severe dementia. In all three areas, neurone loss becomes detectable already at preclinical stages and is clearly manifest at prodromal AD/MCI. At more advanced AD, cell loss is most pronounced in the NbM > LC > layer-II EC. During early AD, however, the extent of cell loss is fairly balanced between all three areas without clear indications for a preference of one area. We can thus not rule out that there is more than one way of spreading from its site of origin or that degeneration even occurs independently at several sites in parallel.

Show MeSH
Related in: MedlinePlus