Dataset Information

CSF proteomics of the APPPS1 Alzheimer mouse model with life long BACE inhibition

ABSTRACT: The earliest defining event in the pathogenesis of Alzheimer´s disease (AD) is the intracerebral deposition of Abeta, which starts at least 20 years before the onset of dementia. The link between Abeta and downstream neurodegeneration leading to dementia remains unclear, a critical gap in knowledge at a time when clinical trials are increasingly shifting to pre-symptomatic disease stages. Consequently, the design of preventive treatment strategies based on biomarkers remains an important challenge. Here, we have analyzed CSF samples from 21.5-month-old APPPS1 and WT mice, with and without BACE inhibition from 1.5 to 21.5 months, using mass spectrometry-based label-free quantification of proteins. Life-long BACE inhibition showed a partial rescue of several CSF protein markers for neurodegeneration such as NEFL and inflammation such as Trem2 or Cst7.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Alzheimer's Disease

SUBMITTER: Stephan Mueller

LAB HEAD: Stefan F. Lichtenthaler

PROVIDER: PXD032782 | Pride | 2022-12-05

REPOSITORIES: Pride

ACCESS DATA

Publications

Experimental evidence for temporal uncoupling of brain Aβ deposition and neurodegenerative sequelae.

Rother Christine C Uhlmann Ruth E RE Müller Stephan A SA Schelle Juliane J Skodras Angelos A Obermüller Ulrike U Häsler Lisa M LM Lambert Marius M Baumann Frank F Xu Ying Y Bergmann Carina C Salvadori Giulia G Loos Maarten M Brzak Irena I Shimshek Derya D Neumann Ulf U Walker Lary C LC Schultz Stephanie A SA Chhatwal Jasmeer P JP Kaeser Stephan A SA Lichtenthaler Stefan F SF Staufenbiel Matthias M Jucker Mathias M

Nature communications 20221128 1

Brain Aβ deposition is a key early event in the pathogenesis of Alzheimer´s disease (AD), but the long presymptomatic phase and poor correlation between Aβ deposition and clinical symptoms remain puzzling. To elucidate the dependency of downstream pathologies on Aβ, we analyzed the trajectories of cerebral Aβ accumulation, Aβ seeding activity, and neurofilament light chain (NfL) in the CSF (a biomarker of neurodegeneration) in Aβ-precursor protein transgenic mice. We find that Aβ deposition incr ...[more]

PMID: 36443293

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Dataset Information

CSF proteomics of the APPPS1 Alzheimer mouse model with life long BACE inhibition

Publications

Experimental evidence for temporal uncoupling of brain Aβ deposition and neurodegenerative sequelae.

Similar Datasets

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