Dataset Information

OCIAD1 contributes to neurodegeneration in Alzheimer's disease by inducing mitochondria dysfunction, neuronal vulnerability and synaptic damages.

ABSTRACT:

Background

Hyperamyloidosis in the brain is known as the earliest neuropathological change and a unique etiological factor in Alzheimer's disease (AD), while progressive neurodegeneration in certain vulnerable brain regions forms the basis of clinical syndromes. It is not clear how early hyperamyloidosis is implicated in progressive neurodegeneration and what factors contribute to the selective brain vulnerability in AD.

Methods

Bioinformatics and experimental neurobiology methods were integrated to identify novel factors involved in the hyperamyloidosis-induced brain vulnerability in AD. We first examined neurodegeneration-specific gene signatures from sporadic AD patients and synaptic protein changes in young transgenic AD mice. Then, we systematically assessed the association of a top candidate gene with AD and investigated its mechanistic role in neurodegeneration.

Findings

We identified the ovary-orientated protein OCIAD1 (Ovarian-Carcinoma-Immunoreactive-Antigen-Domain-Containing-1) as a neurodegeneration-associated factor for AD. Higher levels of OCIAD1, found in vulnerable brain areas and dystrophic neurites, were correlated with disease severity. Multiple early AD pathological events, particularly Aβ/GSK-3β signaling, elevate OCIAD1, which in turn interacts with BCL-2 to impair mitochondrial function and facilitates mitochondria-associated neuronal injury. Notably, elevated OCIAD1 by Aβ increases cell susceptibility to other AD pathological challenges.

Interpretation

Our findings suggest that OCIAD1 contributes to neurodegeneration in AD by impairing mitochondria function, and subsequently leading to neuronal vulnerability, and synaptic damages.

Funding

Ting Tsung & Wei Fong Chao Foundation, John S Dunn Research Foundation, Cure Alzheimer's Fund, and NIH R01AG057635 to STCW.

SUBMITTER: Li X

PROVIDER: S-EPMC6957876 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

OCIAD1 contributes to neurodegeneration in Alzheimer's disease by inducing mitochondria dysfunction, neuronal vulnerability and synaptic damages.

Li Xuping X Wang Lin L Cykowski Matthew M He Tiancheng T Liu Timothy T Chakranarayan Joshua J Rivera Andreana A Zhao Hong H Powell Suzanne S Xia Weiming W Wong Stephen T C STC

EBioMedicine 20200110

<h4>Background</h4>Hyperamyloidosis in the brain is known as the earliest neuropathological change and a unique etiological factor in Alzheimer's disease (AD), while progressive neurodegeneration in certain vulnerable brain regions forms the basis of clinical syndromes. It is not clear how early hyperamyloidosis is implicated in progressive neurodegeneration and what factors contribute to the selective brain vulnerability in AD.<h4>Methods</h4>Bioinformatics and experimental neurobiology methods ...[more]

PMID: 31931285

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Dataset Information

OCIAD1 contributes to neurodegeneration in Alzheimer's disease by inducing mitochondria dysfunction, neuronal vulnerability and synaptic damages.

Background

Methods

Findings

Interpretation

Funding

Publications

OCIAD1 contributes to neurodegeneration in Alzheimer's disease by inducing mitochondria dysfunction, neuronal vulnerability and synaptic damages.

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