Study now links non-mutated Apolipoprotein E to dementia in the aging
brain

Date:
January 26, 2022
Source:
Elsevier
Summary:
Researchers exploring dementia-related proteins in the brain
identified Apolipoprotein E (ApoE) as a key misfolded protein.



FULL STORY ========================================================================== Researchers exploring dementia-related proteins in the brain
identified Apolipoprotein E (ApoE) as a key misfolded protein. About
25% of individuals, and 50% of individuals with Alzheimer disease,
have a genetic mutation, the APOE e4 allele -- a known risk factor for
the disease. The researchers were surprised to find that even in the
brains of patients without the disease- driving APOE e4 allele, ApoE
proteins were strongly enriched in dementia. Their findings appear in
The American Journal of Pathology,published by Elsevier.


========================================================================== "Dementia is very complex, but you can simplify it: the disease is caused
by 'gloppy proteins' in the brain," explained lead investigator Peter
T. Nelson, MD, PhD, Sanders-Brown Center on Aging and Department of
Pathology, University of Kentucky, Lexington, KY, USA. "I'm not making
light of it -- these 'sticky' misfolded proteins often end up destroying
the brain, the mind, the memories and everything else for millions of
people who suffer from dementia. We want to understand specifically which proteins are the problem." The investigators used mass spectrometry to characterize the complete set of proteins, or proteome, from the amygdalae
of 40 participants from the University of Kentucky Alzheimer's Disease
Center autopsy cohort. The amygdala is vulnerable to mis-aggregated
proteins associated with dementia and is often affected even at the
earliest stages of disease. The subjects ranged from cognitively normal
to severe amnestic dementia. Although previous studies have examined
the human amygdala proteome, none have reported on a sample of this size
with dementia subjects and control subjects for comparison.

As anticipated, portions of proteins previously associated with neurodegenerative diseases were found in the brains of patients with
dementia, including proteins called Tau (associated with neurofibrillary tangles), Ab (associated with amyloid plaques), and a-Synuclein
(associated with Lewy Body disease). Ab and a-Synuclein correlated
strongly with clinical diagnosis of dementia. Tau and Ab proteins, but not a-Synuclein, were occasionally detectible in cognitively normal subjects
and those with mild cognitive impairment. Overall, Dr. Nelson observes,
the findings for these proteins were in line with expectations.

The data also revealed a close correlation between dementia diagnosis
and the detection of ApoE peptides in the brain. The correlation with
dementia for ApoE was even stronger than that seen for Tau, Ab, or
a-Synuclein. Moreover, the ApoE peptides were significantly enriched even
in dementia patients who lack the APOE e4 allele. The results emphasize
the relevance of the ApoE protein as an aberrantly aggregated protein
in its own right, rather than just an "upstream" genetic risk factor.

"Our study adds to an evolving appreciation of multiple misfolded
proteins in the human brain and moves the field forward by emphasizing
that ApoE may be a stong contributor to the dementia prototype, even in individuals who do not have the disease-driving version of the APOE gene,"
said Dr. Nelson. "Even in persons lacking the APOE e4 allele, ApoE may
indeed be among the most impactful 'gloppy proteins' in aging brains."
special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by Elsevier. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Jozsef Gal, Yuriko Katsumata, Haining Zhu, Sukanya Srinivasan,
Jing Chen,
Lance Allen Johnson, Wang-Xia Wang, Lesley Renee Golden, Donna M.

Wilcock, Gregory A. Jicha, Matthew D. Cykowski, Peter Tobias Nelson.

Apolipoprotein E Proteinopathy Is a Major Dementia-Associated
Pathologic Biomarker in Individuals with or without the APOE
Epsilon 4 Allele. The American Journal of Pathology, 2021; DOI:
10.1016/j.ajpath.2021.11.013 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220126122408.htm

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