Dataset Information

Cerebrospinal Fluid Alzheimer's Disease Biomarkers in Cerebral Amyloid Angiopathy-Related Inflammation.

ABSTRACT:

Background

Decreased cerebrospinal fluid (CSF) amyloid-? 1-40 (A?40) and amyloid-? 1-42 (A?42) and increased total and phosphorylated tau (t-tau, p-tau) concentrations have been described in cerebral amyloid angiopathy (CAA).

Objective

Our aim was to analyze these biomarkers in patients with CAA-related inflammation (CAA-I).

Methods

We prospectively recruited nine patients with acute phase CAA-I fulfilling Chung criteria. CSF was analyzed for t-tau, p-tau, A?42, and A?40. Data were compared to controls (n?=?14), patients with Alzheimer's disease (AD, n?=?42), CAA (n?=?10), and primary angiitis of the central nervous system (PACNS, n?=?3).

Results

For the CAA-I group, statistically significant differences were: lower A?42 (p?=?0.00053) compared to the control group; lower t-tau (p?=?0.018), p-tau (p?< ?0.001), and A?40 (p?< ?0.001) compared to AD; lower A?42 (p?=?0.027) compared to CAA; lower A?42 (p?=?0.012) compared to PACNS. Nearly significantly lower A?40 (p?=?0.051) and higher t-tau (p?=?0.051) were seen in CAA-I compared to controls.

Conclusion

CSF biomarkers profile similar to that of CAA was observed in CAA-I (with even lower levels of A?42 compared to CAA). Based on our findings, high p-tau seems more specific for AD, whereas low A?42 differentiates CAA-I from CAA, PACNS, and controls, and low A?40 differentiates CAA-I from AD.

SUBMITTER: Renard D

PROVIDER: S-EPMC6294577 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Cerebrospinal Fluid Alzheimer's Disease Biomarkers in Cerebral Amyloid Angiopathy-Related Inflammation.

Renard Dimitri D Wacongne Anne A Ayrignac Xavier X Charif Mahmoud M Fourcade Genevieve G Azakri Souhayla S Le Floch Anne A Bouly Stephane S Marelli Cecilia C Arquizan Caroline C Hirtz Christophe C Gabelle Audrey A Thouvenot Eric E Lehmann Sylvain S

Journal of Alzheimer's disease : JAD 20160101 3

<h4>Background</h4>Decreased cerebrospinal fluid (CSF) amyloid-β 1-40 (Aβ40) and amyloid-β 1-42 (Aβ42) and increased total and phosphorylated tau (t-tau, p-tau) concentrations have been described in cerebral amyloid angiopathy (CAA).<h4>Objective</h4>Our aim was to analyze these biomarkers in patients with CAA-related inflammation (CAA-I).<h4>Methods</h4>We prospectively recruited nine patients with acute phase CAA-I fulfilling Chung criteria. CSF was analyzed for t-tau, p-tau, Aβ42, and Aβ40. D ...[more]

PMID: 26757185

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Project description:Alzheimer's disease (AD) is characterised by pathologic cerebrovascular remodelling. Whether this occurs already before disease onset, as may be indicated by early Braak tau-related cerebral hypoperfusion and blood-brain barrier (BBB) impairment found in previous studies, remains unknown. Therefore, we systematically quantified Braak tau stage- and cerebral amyloid angiopathy (CAA)-dependent alterations in the alpha-smooth muscle actin (α-SMA), collagen, and elastin content of leptomeningeal arterioles, small arteries, and medium-sized arteries surrounding the gyrus frontalis medialis (GFM) and hippocampus (HIPP), including the sulci, of 17 clinically and pathologically diagnosed AD subjects (Braak stage IV-VI) and 28 non-demented control subjects (Braak stage I-IV). GFM and HIPP paraffin sections were stained for general collagen and elastin with the Verhoeff-van Gieson stain; α-SMA and CAA/amyloid β (Aβ) were detected using immunohistochemistry. Significant arterial elastin degradation was observed from Braak stage III onward and correlated with Braak tau pathology (ρ = 0.909, 95% CI 0.370 to 0.990, p < 0.05). This was accompanied by an increase in neutrophil elastase expression by α-SMA-positive cells in the vessel wall. Small and medium-sized arteries exhibited significant CAA-independent α-SMA loss starting between Braak stage I and II-III, along with accumulation of phosphorylated paired helical filament (PHF) tau in the perivascular space of intraparenchymal vessels. α-SMA remained at the decreased level throughout the later Braak stages. In contrast, arterioles exhibited significant α-SMA loss only at Braak stage V and VI/in AD subjects, which was CAA-dependent/correlated with CAA burden (ρ = -0.422, 95% CI -0.557 to -0.265, p < 0.0001). Collagen content was only significantly changed in small arteries. Our data indicate that vessel wall remodelling of leptomeningeal arteries is an early-onset, Braak tau pathology-dependent process unrelated to CAA and AD, which potentially may contribute to downstream CAA-dependent microvascular pathology in AD.

Dataset Information

Cerebrospinal Fluid Alzheimer's Disease Biomarkers in Cerebral Amyloid Angiopathy-Related Inflammation.

Background

Objective

Methods

Results

Conclusion

Publications

Cerebrospinal Fluid Alzheimer's Disease Biomarkers in Cerebral Amyloid Angiopathy-Related Inflammation.

Similar Datasets

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