Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer's disease

Michael Tran Duong; Sandhitsu R Das; Xueying Lyu; Long Xie; Hayley Richardson; Sharon X Xie; Paul A Yushkevich; David A Wolk; Ilya M Nasrallah; Alzheimer’s Disease Neuroimaging Initiative (ADNI)

doi:10.1038/s41467-022-28941-1

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Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer's disease

Journal article

Open access

Peer reviewed

Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer's disease

Michael Tran Duong, Sandhitsu R Das, Xueying Lyu, Long Xie, Hayley Richardson, Sharon X Xie, Paul A Yushkevich, David A Wolk, Ilya M Nasrallah and Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Nature communications, Vol.13(1), pp.1495-1495

03/21/2022

DOI: 10.1038/s41467-022-28941-1

PMCID: PMC8938426

PMID: 35314672

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Abstract

Alzheimer's disease (AD) is defined by amyloid (A) and tau (T) pathologies, with T better correlated to neurodegeneration (N). However, T and N have complex regional relationships in part related to non-AD factors that influence N. With machine learning, we assessed heterogeneity in F-flortaucipir vs. F-fluorodeoxyglucose positron emission tomography as markers of T and neuronal hypometabolism (N ) in 289 symptomatic patients from the Alzheimer's Disease Neuroimaging Initiative. We identified six T/N clusters with differing limbic and cortical patterns. The canonical group was defined as the T/N pattern with lowest regression residuals. Groups resilient to T had less hypometabolism than expected relative to T and displayed better cognition than the canonical group. Groups susceptible to T had more hypometabolism than expected given T and exhibited worse cognitive decline, with imaging and clinical measures concordant with non-AD copathologies. Together, T/N mismatch reveals distinct imaging signatures with pathobiological and prognostic implications for AD.

Biomarkers

Magnetic Resonance Imaging

Alzheimer Disease - diagnostic imaging

Alzheimer Disease - psychology

Amyloid beta-Peptides

Brain - diagnostic imaging

Brain - metabolism

Cognitive Dysfunction

Humans

Neuroimaging - methods

Positron-Emission Tomography - methods

tau Proteins - metabolism

Details

Title: Subtitle: Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer's disease
Creators: Michael Tran Duong - University of Pennsylvania
Sandhitsu R Das - University of Pennsylvania
Xueying Lyu - University of Pennsylvania
Long Xie - University of Pennsylvania
Hayley Richardson - University of Pennsylvania
Sharon X Xie - University of Pennsylvania
Paul A Yushkevich - University of Pennsylvania
David A Wolk - University of Pennsylvania
Ilya M Nasrallah - University of Pennsylvania
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Contributors: HyungSub Shim (Contributor) - University of Iowa, Neurology
Resource Type: Journal article
Publication Details: Nature communications, Vol.13(1), pp.1495-1495
DOI: 10.1038/s41467-022-28941-1
PMID: 35314672
PMCID: PMC8938426
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: P01 AG036694 / NIA NIH HHS RF1 AG069474 / NIA NIH HHS CIHR U01 AG024904 / NIA NIH HHS P30 AG072979 / NIA NIH HHS
Language: English
Date published: 03/21/2022
Academic Unit: Neurology; Psychiatry
Record Identifier: 9984302200702771

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