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Higher Level of Mismatch in APOE?4 Carriers for Amyloid-Beta Peptide Alzheimer's Disease Biomarkers in Cerebrospinal Fluid.

ABSTRACT: Cerebrospinal fluid (CSF) biomarkers are widely used in the diagnosis of dementia. Even though there is a causal correlation between apolipoprotein E ( APOE) genotype and amyloid-beta (A?), the determination of APOE is currently not supported by national or international guidelines. We compared parallel measured CSF biomarkers of two independent laboratories from 126 patients who underwent clinical dementia diagnostics regarding the APOE genotype. APOE ?4 reduces A?1-42 (A?42) and A?42 to A? 1-40 ratio (A?42/40) but not total Tau or phospho-181 Tau CSF levels. Higher discordance rates were observed for A?42 and subsequently for A?42/40 in APOE ?4 carriers compared with noncarriers, and the correlation between the two laboratories was significantly lower for A?42 in APOE ?4 positive patients compared with patients without APOE ?4. These observations demonstrate that the evaluation of CSF A? biomarkers needs to be interpreted carefully in the clinical context. Different immunoassays, disparate cutoff values, and APOE should be respected.

SUBMITTER: Vogelgsang J

PROVIDER: S-EPMC6535906 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Higher Level of Mismatch in APOEε4 Carriers for Amyloid-Beta Peptide Alzheimer's Disease Biomarkers in Cerebrospinal Fluid.

Vogelgsang Jonathan J Vukovich Ruth R Wedekind Dirk D Wiltfang Jens J

ASN neuro 20190101

Cerebrospinal fluid (CSF) biomarkers are widely used in the diagnosis of dementia. Even though there is a causal correlation between apolipoprotein E ( APOE) genotype and amyloid-beta (Aβ), the determination of APOE is currently not supported by national or international guidelines. We compared parallel measured CSF biomarkers of two independent laboratories from 126 patients who underwent clinical dementia diagnostics regarding the APOE genotype. APOE ε4 reduces Aβ1-42 (Aβ<sub>42</sub>) and Aβ< ...[more]

PMID: 31104469

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Project description:BackgroundRecognizing clinical manifestations heralding the development of Alzheimer's disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We aim to characterize the association of body weight change with cognitive changes and AD biomarkers in cognitively unimpaired middle-aged adults.MethodsThis prospective cohort study included data from cognitively unimpaired adults from the ALFA study (n?=?2743), a research platform focused on preclinical AD. Cognitive and anthropometric data were collected at baseline between April 2013 and November 2014. Between October 2016 and February 2020, 450 participants were visited in the context of the nested ALFA+ study and underwent cerebrospinal fluid (CSF) extraction and acquisition of positron emission tomography images with [18F]flutemetamol (FTM-PET). From these, 408 (90.1%) were included in the present study. We used data from two visits (average interval 4.1?years) to compute rates of change in weight and cognitive performance. We tested associations between these variables and between weight change and categorical and continuous measures of CSF and neuroimaging AD biomarkers obtained at follow-up. We classified participants with CSF data according to the AT (amyloid, tau) system and assessed between-group differences in weight change.ResultsWeight loss predicted a higher likelihood of positive FTM-PET visual read (OR 1.27, 95% CI 1.00-1.61, p?=?0.049), abnormal CSF p-tau levels (OR 1.50, 95% CI 1.19-1.89, p?=?0.001), and an A+T+ profile (OR 1.64, 95% CI 1.25-2.20, p?=?0.001) and was greater among participants with an A+T+ profile (p?<?0.01) at follow-up. Weight change was positively associated with CSF A?42/40 ratio (??=?0.099, p?=?0.032) and negatively associated with CSF p-tau (??=?-?0.141, p?=?0.005), t-tau (??=?-?0.147 p?=?0.004) and neurogranin levels (??=?-?0.158, p?=?0.002). In stratified analyses, weight loss was significantly associated with higher t-tau, p-tau, neurofilament light, and neurogranin, as well as faster cognitive decline in A+ participants only.ConclusionsWeight loss predicts AD CSF and PET biomarker results and may occur downstream to amyloid-? accumulation in preclinical AD, paralleling cognitive decline. Accordingly, it should be considered as an indicator of increased risk of AD-related cognitive impairment.Trial registrationNCT01835717 , NCT02485730 , NCT02685969 .

Dataset Information

Higher Level of Mismatch in APOE?4 Carriers for Amyloid-Beta Peptide Alzheimer's Disease Biomarkers in Cerebrospinal Fluid.

Publications

Higher Level of Mismatch in APOEε4 Carriers for Amyloid-Beta Peptide Alzheimer's Disease Biomarkers in Cerebrospinal Fluid.

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