Apolipoprotein B is a novel marker for early tau pathology in Alzheimer's disease

Abstract

Introduction:We examine the role of brain apolipoprotein B (apoB) as a putative marker of early tau pathology and cognitive decline. Methods:Cerebrospinal fluid (CSF) samples from cognitively normal and Alzheimer's disease (AD) participants were collected to measure protein levels of apoB and AD biomarkers amyloid beta (Aβ), t-tau and p-tau, as well as synaptic markers GAP43, SYNAPTOTAGMIN-1, synaptosome associated protein 25 (SNAP-25), and NEURO-GRANIN. CSF apoB levels were contrasted with positron emission tomography (PET) scan measures of Aβ (18F-NAV4694) and Tau (flortaucipir) along with cognitive assessment alterations over 6 to 8 years.Results: CSF apoB levels were elevated in AD participants and correlated with t-tau, p-tau, and the four synaptic markers in pre-symptomatic individuals. In the latter, CSF apoB levels correlated with PET flortaucipir-binding in entorhinal, parahippocampal, and fusiform regions. Baseline CSF apoB levels were associated with longitudinal visuospatial cognitive decline.Discussion: CSF apoB markedly associates with early tau dysregulation in asymptomatic subjects and identifies at-risk individuals predisposed to develop visuospatial cognitive decline over time.

Serum lipid traits and the risk of dementia: A cohort study of 254,575 women and 214,891 men in the UK Biobank

“…individuals. ApoB from cerebrospinal fluid sample was identified as an important marker for tau pathology and cognitive decline, 27 which reinforces the need for considering apolipoproteins in clinical practice, and these findings may also be useful for designing more effective drug interventions. Proatherogenic and antiatherogenic lipoprotein measurements, and their ratios, may capture important clinical risk information on dementia risk variations, as has been highlighted for CVD outcomes previously.…”

Plasma high‐density lipoprotein cargo is altered in Alzheimer's disease and is associated with regional brain volume

“…In the CSF ApoE and ApoJ are the main apolipoproteins, while ApoA‐I, the main constituent of plasma HDL is not produced in the central nervous system. However, damage to the blood‐brain barrier (BBB), common in AD, allows ApoC‐III, not usually produced in the brain, to be detected in the CSF (Picard et al, 2022), while ApoA‐I can be transported across the BBB at the choroid plexus (Stukas et al, 2014). In general, lipid dysregulation in the brain affects AD like many other neurodegenerative diseases.…”

Association of a Total Cholesterol Polygenic Score with Cholesterol Levels and Pathological Biomarkers across the Alzheimer’s Disease Spectrum

“…ApoB-containing lipoproteins such as LDL and VLDL have been associated with vascular or mixed dementia [73] in contrast to total cholesterol, which is the one clearly associated with AD risk. The observed apoB/phosphotau association in pre-symptomatic AD is markedly modulated by the presence of the APOE-ε4 allele but not by the passage of peripheral apoB into the CNS [74]; supporting the notion that the total cholesterol could act more as a surrogate biomarker for APOE-ε4 mediated effects than a direct player in the pathophysiological process. This would be consistent with the above results showing that genetic variants, other than the genetic variants resulting in the APOE-ε4 isoform, strongly correlate with TC levels but fail to associate with AD pathology.…”