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[P4–068]: THREE NOVEL PATHOGENIC VARIANTS IN CLUSTERIN (CLU) ASSOCIATED WITH EARLY‐ONSET ALZHEIMER DISEASE
Author(s) -
Van Giau Vo,
Bagyinszky Eva,
Shim Kyu Hwan,
Yang Youngsoon,
Youn Young Chul,
An Seong Soo,
Kim Sang Yun
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1933
Subject(s) - psen1 , clusterin , genetics , exome sequencing , missense mutation , gene , biology , phenotype , exome , disease , early onset alzheimer's disease , coding region , presenilin , medicine , alzheimer's disease , apoptosis
type rats triggered its self-production as well as Ab1-42, thus demonstrating the peptide’s pivotal signalling role in AD. Next, we explored the suitability of AChE peptide as biomarker by investigating the association between the peptide and AD pathology through the measurement of AChE peptide levels in key brain regions (cerebral cortex, hippocampus, locus coeruleus) as well as in cerebrospinal fluid (CSF). In CSF, in both control and AD brains, six AChE peptide aggregates were detected (at 25, 30, 40, 50, 90 and 130 KDa) and three aggregates were found in the brain (30, 40 and 50 KDa). After peptide quantification, one aggregate (30KDa) showed a highly significant decrease in the locus coeruleus in AD. In contrast, all individual AChE peptide aggregates in post-mortem CSF and two AChE peptide aggregates in ex-vivo CSF were significantly increased in AD with levels much higher than in the brain, for both controls and AD cases. Conclusions: AChE peptide may have potential as a biomarker in CSF for the pathological process underlying Alzheimer’s disease.