Congratulations! Our lab member Dr. Yue Cai and Ph.D. student Jie Yang published their new work "Revealing white matter hyperintensities-related faster posterior cortical tau accumulation in Alzheimer’s Disease" in Molecular Neurodegeneration. More information please refer to https://link.springer.com/article/10.1186/s13024-026-01013-4#Abs1

Abstract:

Background：Alzheimer’s disease (AD) is a multifactorial disorder in which cerebrovascular abnormalities frequently co-occur with β-amyloid (Aβ) and tau pathology. White matter hyperintensities (WMH), a common marker of cerebral small vessel disease, are associated with cognitive impairment and are highly prevalent across the AD continuum. However, the extent to which WMH burden is associated with spatial patterns of tau pathology and its longitudinal accumulation remains unclear.

Methods: We examined 1,455 participants with Aβ PET, tau PET, T2-FLAIR MRI, and cognitive assessments from four independent cohorts: ADNI (n = 710), A4/LEARN (n = 440), GHABS (n = 249), and PREVENT-AD (n = 56). Resting-state functional MRI data were available in subsets of ADNI and A4, and CSF SomaScan proteomic data were available in ADNI and PREVENT-AD. Associations of WMH burden with longitudinal tau accumulation and network-based tau propagation were examined. A data-driven approach was used to identify distinct tau subtypes. WMH burden, tau accumulation, and clinical and biological characteristics were evaluated across subtypes.

Results: Greater total WMH burden was associated with faster tau accumulation (ADNI, A4) or higher subsequent tau burden (GHABS) in the temporal meta-ROI among Aβ-positive (A+) individuals. These associations were attenuated after accounting for Aβ burden. However, greater WMH burden, particularly in the occipital lobe, remained significantly associated with faster tau accumulation and network-based tau propagation in occipital regions after adjustment for Aβ burden. An occipital-dominant tau subtype was identified, characterized by greater occipital than parietal tau burden. This subtype showed more widespread associations between WMH and tau accumulation, an older estimated age of Aβ positivity onset, and a higher prevalence of hypertension, together with slower global tau accumulation and cognitive decline than the parietal-dominant subtype. CSF proteomic analyses further identified vascular and extracellular matrix pathways related to tenascin-C (TNC) in the occipital-dominant subtype.

Conclusions: Greater WMH burden was associated with faster tau accumulation and network-based tau propagation, with the most consistent associations involving occipital regions. These findings suggest that the association between WMH burden and occipital tau progression may reflect vascular contributions to regional tau vulnerability in the context of AD pathology.

Keywords: Alzheimer's disease; Neuroscience; Neurological Disorders; White matter injury; Neurology; White matter disease