Autosomal dominant and sporadic late onset Alzheimer's disease share a common in vivo pathophysiology

Abstract

The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of 'sporadic' late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI and amyloid PET data, as well as CSF concentrations of amyloid-β42, amyloid-β40, tau and tau phosphorylated at position 181, in 292 carriers of pathogenic variants for Alzheimer's disease from the Dominantly Inherited Alzheimer Network, with corresponding data from 559 participants from the Alzheimer's Disease Neuroimaging Initiative. Imaging data and CSF samples were reprocessed as appropriate to guarantee uniform pipelines and assays. Data analyses yielded rates of change before and after symptomatic onset of Alzheimer's disease, allowing the alignment of the ∼ 30-year age difference between the cohorts on a clinically meaningful anchor point, namely the participant age at symptomatic onset. Biomarker profiles were similar for both autosomal dominant Alzheimer's disease and late onset Alzheimer's disease. Both groups demonstrated accelerated rates of decline in cognitive performance and in regional brain volume loss after symptomatic onset. Although amyloid burden accumulation as determined by PET was greater after symptomatic onset in autosomal dominant Alzheimer's disease than in late onset Alzheimer's disease participants, CSF assays of amyloid-β42, amyloid-β40, tau and p-tau181 were largely overlapping in both groups. Rates of change in cognitive performance and hippocampal volume loss after symptomatic onset were more aggressive for autosomal dominant Alzheimer's disease participants. These findings suggest a similar pathophysiology of autosomal dominant Alzheimer's disease and late onset Alzheimer's disease, supporting a shared pathobiological construct.

RAS ID

52358

Document Type

Journal Article

Date of Publication

10-21-2022

Volume

145

Issue

10

Funding Information

Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA)

Further funding information available at:

https://doi.org/10.1093/brain/awac181

PubMed ID

35580594

School

School of Medical and Health Sciences

Copyright

subscription content

Publisher

Oxford Academic

Comments

Morris, J. C., Weiner, M., Xiong, C., Beckett, L., Coble, D., Saito, N., ... & Alzheimer’s Disease Neuroimaging Initiative. (2022). Autosomal dominant and sporadic late onset Alzheimer disease share a common in vivo pathophysiology. Brain, 145(10), 3594-3607. https://doi.org/10.1093/brain/awac181

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Link to publisher version (DOI)

10.1093/brain/awac181