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Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism.

Mattsson N, Bremell D, Anckarsäter R, Blennow K, Anckarsäter H, Zetterberg H, Hagberg L - BMC Neurol (2010)

Bottom Line: CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage.In the prospective study, LNB patients had low levels of CSF alpha-sAPP, beta-sAPP and P-tau at baseline, which all increased towards normal at follow-up.CSF levels of alpha-sAPP, beta-sAPP and P-tau are decreased in acute infection and increase after treatment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. niklas.mattsson@neuro.gu.se

ABSTRACT

Background: The metabolism of amyloid precursor protein (APP) and beta-amyloid (Abeta) is widely studied in Alzheimer's disease, where Abeta deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid metabolism in patients with Lyme neuroborreliosis (LNB).

Methods: The first part of the study was a cross-sectional cohort study in 61 patients with acute facial palsy (19 with LNB and 42 with idiopathic facial paresis, Bell's palsy) and 22 healthy controls. CSF was analysed for the beta-amyloid peptides Abeta38, Abeta40 and Abeta42, and the amyloid precursor protein (APP) isoforms alpha-sAPP and beta-sAPP. CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage. The second part of the study was a prospective cohort-study in 26 LNB patients undergoing consecutive lumbar punctures before and after antibiotic treatment to study time-dependent dynamics of the biomarkers.

Results: In the cross-sectional study, LNB patients had lower levels of CSF alpha-sAPP, beta-sAPP and P-tau, and higher levels of CSF NFL than healthy controls and patients with Bell's palsy. In the prospective study, LNB patients had low levels of CSF alpha-sAPP, beta-sAPP and P-tau at baseline, which all increased towards normal at follow-up.

Conclusions: Amyloid metabolism is altered in LNB. CSF levels of alpha-sAPP, beta-sAPP and P-tau are decreased in acute infection and increase after treatment. In combination with earlier findings in multiple sclerosis, cerebral SLE and HIV with cerebral engagement, this points to an influence of neuroinflammation on amyloid metabolism.

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Related in: MedlinePlus

CSF levels of α-sAPP and β-sAPP in LNB patients with follow-up and controls. Horizontal lines indicate mean values. CSF α-sAPP (panel A) and β-sAPP (panel B) were reduced in LNB patients compared to controls at baseline, and increased at follow-up.
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Figure 2: CSF levels of α-sAPP and β-sAPP in LNB patients with follow-up and controls. Horizontal lines indicate mean values. CSF α-sAPP (panel A) and β-sAPP (panel B) were reduced in LNB patients compared to controls at baseline, and increased at follow-up.

Mentions: In the longitudinal study, LNB patients had lower baseline levels of α-sAPP and β-sAPP (Figure 2) and Aβ peptides than controls (Table 3). α-sAPP and β-sAPP increased after treatment (Figure 2), while Aβ levels were unaffected (Table 3). Conversely to what was seen in the cross-sectional study, α-sAPP and β-sAPP correlated to all Aβ peptides in LNB in the longitudinal study (R = .71-.98, P < .001), but not in controls (P > .05).


Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism.

Mattsson N, Bremell D, Anckarsäter R, Blennow K, Anckarsäter H, Zetterberg H, Hagberg L - BMC Neurol (2010)

CSF levels of α-sAPP and β-sAPP in LNB patients with follow-up and controls. Horizontal lines indicate mean values. CSF α-sAPP (panel A) and β-sAPP (panel B) were reduced in LNB patients compared to controls at baseline, and increased at follow-up.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2902447&req=5

Figure 2: CSF levels of α-sAPP and β-sAPP in LNB patients with follow-up and controls. Horizontal lines indicate mean values. CSF α-sAPP (panel A) and β-sAPP (panel B) were reduced in LNB patients compared to controls at baseline, and increased at follow-up.
Mentions: In the longitudinal study, LNB patients had lower baseline levels of α-sAPP and β-sAPP (Figure 2) and Aβ peptides than controls (Table 3). α-sAPP and β-sAPP increased after treatment (Figure 2), while Aβ levels were unaffected (Table 3). Conversely to what was seen in the cross-sectional study, α-sAPP and β-sAPP correlated to all Aβ peptides in LNB in the longitudinal study (R = .71-.98, P < .001), but not in controls (P > .05).

Bottom Line: CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage.In the prospective study, LNB patients had low levels of CSF alpha-sAPP, beta-sAPP and P-tau at baseline, which all increased towards normal at follow-up.CSF levels of alpha-sAPP, beta-sAPP and P-tau are decreased in acute infection and increase after treatment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. niklas.mattsson@neuro.gu.se

ABSTRACT

Background: The metabolism of amyloid precursor protein (APP) and beta-amyloid (Abeta) is widely studied in Alzheimer's disease, where Abeta deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid metabolism in patients with Lyme neuroborreliosis (LNB).

Methods: The first part of the study was a cross-sectional cohort study in 61 patients with acute facial palsy (19 with LNB and 42 with idiopathic facial paresis, Bell's palsy) and 22 healthy controls. CSF was analysed for the beta-amyloid peptides Abeta38, Abeta40 and Abeta42, and the amyloid precursor protein (APP) isoforms alpha-sAPP and beta-sAPP. CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage. The second part of the study was a prospective cohort-study in 26 LNB patients undergoing consecutive lumbar punctures before and after antibiotic treatment to study time-dependent dynamics of the biomarkers.

Results: In the cross-sectional study, LNB patients had lower levels of CSF alpha-sAPP, beta-sAPP and P-tau, and higher levels of CSF NFL than healthy controls and patients with Bell's palsy. In the prospective study, LNB patients had low levels of CSF alpha-sAPP, beta-sAPP and P-tau at baseline, which all increased towards normal at follow-up.

Conclusions: Amyloid metabolism is altered in LNB. CSF levels of alpha-sAPP, beta-sAPP and P-tau are decreased in acute infection and increase after treatment. In combination with earlier findings in multiple sclerosis, cerebral SLE and HIV with cerebral engagement, this points to an influence of neuroinflammation on amyloid metabolism.

Show MeSH
Related in: MedlinePlus