Year: 2026
Type: article
Study design: Observational Study
Abstract: In this study, we investigated longitudinal tau spreading in 23 amyloid-positive individuals with early-stage posterior cortical atrophy (PCA), a clinical syndrome typically characterized by progressive visual cognitive deficits emerging largely from underlying Alzheimer’s disease-related tau deposition in posterior cortical areas. Each PCA participant underwent structural MRI and 18 F-Flortaucipir PET at baseline and follow-up (mean interval between baseline and follow-up PET = 1.17 ± 0.29 years). Using directional regression analysis (i.e., a regression-based model testing temporal directionality in tau spread), we quantified how tau epicenters (top 10% regions by baseline tau) predicted longitudinal tau accumulation. Seed-based analysis revealed evidence supporting the role of posterior cortical epicenters in the visual and dorsal attention networks (DAN), showing directional spreading of tau to anterior DAN nodes and the default mode network (DMN), with the largest effects in anterior DAN regions. Complementary graph theory analysis identified the visual network and posterior DMN as hubs of tau spread. These findings collectively suggest that longitudinal tau spread in PCA follows hierarchical progression from primary epicenters within the visual network and DAN to secondary epicenters, including the posterior DMN, possibly mediated by dynamic connectivity reorganization as primary epicenters become saturated with tau pathology.
Source: npj Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Alzheimer's Association, Massachusetts General Hospital, Centre d'Imagerie BioMédicale, National Institutes of Health, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, National Institute on Aging, National Institute on Deafness and Other Communication Disorders, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering
Awards: G1220546045, Imaging tau, amyloid, and neurodegeneration in PPA, G3549079774, Neuromodulation of brain network function in preclinical and prodromal Alzheimer's Disease, Tau and cortical functional network dynamics in Alzheimer's disease, Dissociating the mechanisms of Tau PET and cortical atrophy underlying memory deficits in typical and atypical prodromal Alzheimer's disease, Toward Personalized Prognosis and Outcomes in Primary Progressive Aphasia, G639043084, G6876577119, Massachusetts Alzheimer's Disease Research Center, Center for Functional Imaging Technologies, Neurogenetic contributions to the spread of tau pathology in sporadic early-onset Alzheimer's disease, G868551019, G9000239533, Robust detection of atrophy over short intervals in AD and FTLD, New Approaches to Dementia Heterogeneity, Reimagining Precision Medicine Approaches to AD Diagnosis, Massachusetts Alzheimer's Disease Research Center (MADRC)
OpenAlex ID: W7165154981