Biomarkers.

Background: There is a strong link between tau and progression of Alzheimer's disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial heterogeneity of tau in typical AD, validating this connectivity-based tau spreading model in AD variants with distinct tau deposition patterns is crucial.

Biomarkers.

Background: Amnestic mild cognitive impairment and Alzheimer's disease (aAD) exhibit degeneration of white matter (WM) tracts preceding overt cognitive decline. However, WM changes in non-amnestic AD (naAD) are understudied. We hypothesized patterns of WM degeneration would differ between aAD and naAD.

Biomarkers.

Background: Frontotemporal lobar degeneration (FTLD) is defined neuropathologically by misfolded tau (FTLD-tau) or TAR DNA-binding protein of 43 kDa (FTLD-TDP). However, we lack biomarkers that can distinguish them in vivo which is a major barrier to effective disease-modifying treatment trials. Based on neuropathological evidence of distinct patterns of cellular degeneration, more prominent in white matter (WM) for FTLD-tau relative to FTLD-TDP, we hypothesized that diffusion MRI (dMRI) measures of white matter microstructure would help dissociate FTLD-tau and FTLD-TDP during life.

Biomarkers.

Background: Alzheimer's disease (AD) is clinically heterogeneous, and can manifest as amnestic or non-amnestic dementia, or be pre-manifest in persons with normal cognition (NormCog). Utility of plasma biomarkers to diagnose AD and prognose cognitive decline must be evaluated in a clinically heterogeneous population representative of the AD spectrum. We investigate pathological and cognitive correlates of plasma phosphorylated tau 181 (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) across AD and AD-related dementias (ADRD).

Biomarkers.

Background: The human brain is organized in dense and distinct intrinsic networks that are topographically arranged and mediate particular cognitive functions. The characteristic of intrinsic network organization that supports this functional specialization of cognitive domains is known as modular segregation. Neurodegeneration is associated with changes in brain network organization that contribute to cognitive decline among healthy older adults but network segregation has rarely been studied in behavioral variant frontotemporal dementia (bvFTD).