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ATAD3A heterzygous AD mouse brain, LC-MS

ABSTRACT: Predisposition to Alzheimer's disease (AD) may arise from lipid metabolism perturbation, however, the underlying mechanism remains elusive. Here, we identify ATAD3A, a mitochondrial AAA-ATPase, as a molecular switch that links cholesterol metabolism impairment to AD phenotypes. In neuronal models of AD, the 5XFAD mouse model and post-mortem AD brains, ATAD3A is oligomerized and accumulated at the mitochondria-associated ER membranes (MAMs), where it induces cholesterol accumulation. Suppressing ATAD3A oligomerization by heterozygous ATAD3A knockout normalizes brain cholesterol turnover and MAM integrity, suppresses APP processing and synaptic loss, and consequently reduces AD neuropathology and cognitive deficits in AD transgenic mice. These findings reveal a role for ATAD3A oligomerization in AD pathogenesis and suggest ATAD3A as a potential therapeutic target for AD.

INSTRUMENT(S): LTQ, LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Xin Qi

LAB HEAD: Xin Qi

PROVIDER: PXD031523 | Pride | 2022-02-11

REPOSITORIES: pride

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ATAD3A heterzygous AD mouse brain, LC-MS

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