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Influences of amyloid-β and tau on white matter neurite alterations in dementia with Lewy bodies.

Published version
Peer-reviewed

Repository DOI


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Authors

Mak, Elijah 
Reid, Robert I 
Przybelski, Scott A 
Lesnick, Timothy G 
Schwarz, Christopher G  ORCID logo  https://orcid.org/0000-0002-1466-8357

Abstract

Dementia with Lewy bodies (DLB) is a neurodegenerative condition often co-occurring with Alzheimer's disease (AD) pathology. Characterizing white matter tissue microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) may help elucidate the biological underpinnings of white matter injury in individuals with DLB. In this study, diffusion tensor imaging (DTI) and NODDI metrics were compared in 45 patients within the dementia with Lewy bodies spectrum (mild cognitive impairment with Lewy bodies (n = 13) and probable dementia with Lewy bodies (n = 32)) against 45 matched controls using conditional logistic models. We evaluated the associations of tau and amyloid-β with DTI and NODDI parameters and examined the correlations of AD-related white matter injury with Clinical Dementia Rating (CDR). Structural equation models (SEM) explored relationships among age, APOE ε4, amyloid-β, tau, and white matter injury. The DLB spectrum group exhibited widespread white matter abnormalities, including reduced fractional anisotropy, increased mean diffusivity, and decreased neurite density index. Tau was significantly associated with limbic and temporal white matter injury, which was, in turn, associated with worse CDR. SEM revealed that amyloid-β exerted indirect effects on white matter injury through tau. We observed widespread disruptions in white matter tracts in DLB that were not attributed to AD pathologies, likely due to α-synuclein-related injury. However, a fraction of the white matter injury could be attributed to AD pathology. Our findings underscore the impact of AD pathology on white matter integrity in DLB and highlight the utility of NODDI in elucidating the biological basis of white matter injury in DLB.

Description

Funder: National Institute of Health, R01 AG40042

Keywords

32 Biomedical and Clinical Sciences, 5202 Biological Psychology, 5204 Cognitive and Computational Psychology, 3209 Neurosciences, 52 Psychology, Dementia, Alzheimer's Disease, Lewy Body Dementia, Cerebrovascular, Alzheimer's Disease Related Dementias (ADRD), Neurosciences, Neurodegenerative, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Vascular Cognitive Impairment/Dementia, Biomedical Imaging, Brain Disorders, 2.1 Biological and endogenous factors, Neurological

Journal Title

NPJ Parkinsons Dis

Conference Name

Journal ISSN

2373-8057
2373-8057

Volume Title

10

Publisher

Springer Science and Business Media LLC