Alzheimer Dementia: Alzheimer's disease, apolipoprotein B is a new marker of early tau pathology

Elevated plasma cholesterol level is one of the established vascular risk factors for sporadic Alzheimer’s disease (SAD) , and the blood contains lipoprotein B (apoB) and low-density lipoprotein (LDL) in middle age.
It is associated with an increased risk of SAD, which makes LDL nominated as an important differential factor in the etiology of dementia
.

Cholesterol blood vessel

In contrast, high cholesterol in old age does not seem to be related to any form of dementia or cognitive decline
.

In recent months, two parallel pieces of evidence have shown that circulating LDL levels play a positive role in the pathogenesis of early-onset familial Alzheimer’s disease (EOAD)

The association of EOAD has been shown to be largely driven by rare coding mutations present in the APOB gene, which indicates the pathophysiological role of low-density lipoprotein bound to apoB
.

This indicates the pathophysiological role of low-density lipoprotein bound to apoB
.

At the genetic and molecular level, several apolipoproteins have been directly related to the etiology of SAD, including APOE, clusterin (CLU or apoJ), and now APOB
.

Apolipoproteins, such as apoB, apoE, and apoJ, as well as apoC3 and apoA1, combine to form soluble lipoproteins (such as high-density lipoprotein [HDL]), which act as lipid transport vehicles in blood and CSF

Although there is no detectable low-density lipoprotein level in the cerebrospinal fluid, a large amount of apoB protein can be detected by sensitive magnetic fluorescence detection, while the brain APOB messenger RNA (mRNA) can be easily detected by RNA-Seq technology
.

SAD patients usually show increased blood apoB and low-density lipoprotein levels, while high-density lipoprotein levels decreased, which was positively correlated with brain tissue amyloid β (Aβ-42 levels in postmortem studies
.

In transgenic mice, lifelong Apob overexpression can induce a significant decline in the cognitive ability of the Morris water maze in middle age, accompanied by the accumulation of apoB protein in the cerebral blood vessels, and obvious astrogliosis at the same time
.

These observations prompted people to study the neurobiology of APOB genes and related proteins in the brains of cognitively accessible "high-risk" subjects

These observations prompted people to study the neurobiology of APOB genes and related proteins in the brains of cognitively accessible "high-risk" subjects

In this way, Cynthia Picard and others of Douglas Mental Health University Institute in Canada studied the role of cerebral lipoprotein B (apoB) as a hypothetical marker of early tau pathology and cognitive decline
.

They collected samples of cerebrospinal fluid (CSF) from participants with normal cognition and Alzheimer’s disease (AD), and measured the protein levels of apoB and AD biomarkers amyloid β (Aβ), t-tau and p-tau, as well as Contact markers GAP43, SYNAPTOTAGMIN-1, synaptosome-associated protein 25 (SNAP-25) and NEUROGRANIN
.

CSF apoB levels were compared with Aβ (18F-NAV4694) and Tau (flortaucipir) measured by positron emission tomography (PET), and cognitive assessment changes over 6 to 8 years
.

They found that CSF apoB levels in AD participants were elevated and correlated with t-tau, p-tau, and four synaptic markers in asymptomatic individuals
.

The level of CSF apoB in AD participants was elevated and correlated with t-tau, p-tau, and four synaptic markers in pre-asymptomatic individuals
.

In the latter, CSF apoB levels are associated with PET flortaucipir binding in the medial, parahippocampus, and fusiform domains
.

The baseline CSF apoB level is related to the decline of longitudinal visual and spatial cognitive ability

The important significance of this study lies in the discovery: CSF apoB is significantly related to the early tau imbalance in asymptomatic subjects, and it has identified the high-risk population that is likely to develop visual and spatial cognitive decline over time
.

CSF apoB is significantly related to early tau dysregulation in asymptomatic subjects, and identifies high-risk groups who are prone to develop visual and spatial cognitive decline over time
.

Original source:
Picard C, Nilsson N, Labonté A, et al.

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

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

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