Earlier Alzheimer’s disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading

Abstract

In Alzheimer’s disease (AD), younger symptom onset is associated with accelerated disease progression and tau spreading, yet the mechanisms underlying faster disease manifestation are unknown. To address this, we combined resting-state fMRI and longitudinal tau-PET in two independent samples of controls and biomarker-confirmed AD patients (ADNI/BioFINDER, n = 240/57). Consistent across both samples, we found that younger symptomatic AD patients showed stronger tau-PET in globally connected fronto-parietal hubs, i.e., regions that are critical for maintaining cognition in AD. Stronger tau-PET in hubs predicted faster subsequent tau accumulation, suggesting that tau in globally connected regions facilitates connectivity-mediated tau spreading. Further, stronger tau-PET in hubs mediated the association between younger age and faster tau accumulation in symptomatic AD patients, which predicted faster cognitive decline. These independently validated findings suggest that younger AD symptom onset is associated with stronger tau pathology in brain hubs, and accelerated tau spreading throughout connected brain regions and cognitive decline.

In Vivo Tau Burden Is Associated with Abnormal Brain Functional Connectivity in Alzheimer’s Disease: A 18F-Florzolotau Study

“…Our previous study performed individually specified PLFCS to quantitatively characterize the decrease degree and the PLFCS of the left middle temporal gyrus that yielded a powerful diagnostic efficacy of 80% for categorizing SCD from NC. Moreover, significant gray matter volume reductions, altered FC pattern and density, together with severely decreased amplitude of low-frequency fluctuation in the left MTG have been reported in previous studies on MCI [ 40 , 41 , 42 , 43 ]. These findings indicated that the MTG was a crucial network node with rich connections, and it could be a promising target in studies of the AD continuum.…”

“…These findings indicated that the MTG was a crucial network node with rich connections, and it could be a promising target in studies of the AD continuum. In addition to MTG, other regional connectome alterations such as hippocampal connectivity [ 17 ] and frontoparietal control network hubs [ 43 ] were also reported on MCI and AD, and some were proven to be related to tau pathology in disease progression [ 44 ]. Therefore, other FC assessments would be used to estimate the functional abnormality and its relationship with tau burden, and additional regional connectome influenced by cognition impairment-related pathological alterations would be analyzed in further studies, which might offer new insights into the pathological interpretation of the relationship between tau accumulation and the functional connectivity and find more potential biomarkers in the AD continuum.…”

The Feasibility of Early Alzheimer’s Disease Diagnosis Using a Neural Network Hybrid Platform

“…Fabrication of the platform was based on sphere lithography [ 26 ]. A periodic gold nano pyramid structure, with a diameter of 200 nm, was fabricated by a wafer-scale, bottom-up templating technology [ 37 ].…”

“…CSF provides a means to assess neurodegenerative processes in the brain through the identification of disease-associated molecules. These molecules most often are proteins or protein fragments, including the amyloid β-protein (Aβ) and tau [ 20 , 22 , 23 , 24 , 25 , 26 , 27 ], which are amenable to analysis using a variety of techniques, including surface-enhanced Raman spectroscopy (SERS) [ 28 , 29 ]. The raw spectral information collected from CSF covers a huge multi-dimensional dataset.…”

Fats, Friends or Foes: Investigating the Role of Short- and Medium-Chain Fatty Acids in Alzheimer’s Disease

“…Neurofibrillary tangles (NFTs) are another kind of aggregated protein seen in the brains of AD patients [ 20 ]. These NFTs consist of neuronal hyper-phosphorylated filaments of the microtubule-associated protein tau MAPT [ 21 ].…”