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Publication

Lipid-dependent deposition of alpha-synuclein and Tau on neuronal Secretogranin II-positive vesicular membranes with age.

Oeystein R Brekk | Alyssa Moskites | Ole Isacson | Penelope J Hallett

Scientific reports | 2018

This report demonstrates insoluble alpha-synuclein (aSYN)+ aggregates in human sporadic Parkinson's disease (PD) midbrain that are linearly correlated with loss of glucocerebrosidase (GCase) activity. To identify early protein-lipid interactions that coincide with loss of lipid homeostasis, an aging study was carried out in mice with age-dependent reductions in GCase function. The analysis identified aberrant lipid-association by aSYN and hyperphosphorylated Tau (pTau) in a specific subset of neurotransmitter-containing, Secretogranin II (SgII)+ large, dense-core vesicles (LDCVs) responsible for neurotransmission of dopamine and other monoamines. The lipid vesicle-accumulation was concurrent with loss of PSD-95 suggesting synaptic destabilization. aSYN overexpression in the absence of lipid deregulation did not recapitulate the abnormal association with SgII+ vesicles. These results show lipid-dependent changes occur with age in neuronal vesicular membrane compartments that accumulate lipid-stabilized aSYN and pTau.

Pubmed ID: 30315256 RIS Download

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Associated grants

Agency: NIA NIH HHS, United States
Id: R01 AG060195
Agency: NINDS NIH HHS, United States
Id: R01 NS092667
Agency: U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging), International
Id: R01AG060195
Agency: U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS), International
Id: R01NS092667

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