Biomarkers.

Background: The amygdala is a hotspot for neuropathologies; however, it is unclear 1) which neuropathologies lead to amygdala neurodegeneration, 2) what specific amygdala subnuclei are affected, and 3) if the neuropathologies related to amygdala volume are local (inside the amygdala), or distal (in other regions). We investigate the relationships between different neuropathologies (tau, amyloid-β [Aβ], α-synuclein [α-syn], and transactive response DNA-binding protein 43 [TDP-43]) and amygdala volumes.

Method: We analyzed postmortem data from 73 individuals with and without neurodegenerative diseases (age: 77±11 [45-101] years; 26 [36%] females; 51 [70%] cognitively impaired).

Biomarkers.

Background: The medial temporal lobe (MTL) is the epicenter of both primary and concomitant molecular pathologies in Alzheimer's disease (AD). The intricate anatomy of the MTL has been the subject of extensive study over the past two centuries. However, current PET and MRI AD biomarkers use often crude parcellations of the MTL that have not been sufficiently validated vis-à-vis anatomical ground truth.

Public Health.

Background: Prior research suggests living in an advantaged community in childhood is protective for late-life cognition and MRI-derived markers of brain health, independent of individual socioeconomic status. We examined the extent to which this effect is mediated by midlife hypertension status.

Method: KHANDLE and STAR are racially/ethnically diverse cohorts of older adults residing in northern California.

Biomarkers.

Background: Hippocampal Sclerosis of aging (HS) refers to age-related selective neuronal loss and gliosis in hippocampal cornu ammonis 1 (CA1) and subiculum that is out of proportion to tau pathology in Alzheimer's Disease (AD). HS is related to cognitive decline and memory impairments separately from other neurodegenerative pathologies. To date, in vivo imaging biomarkers of HS of aging are non-existent, and their development would greatly improve diagnosis and prognosis in memory clinics.

Developing Topics.

Background: The anterior portion of the MTL is one of the first regions targeted by pathology in sporadic Alzheimer's disease (AD) indicating the potential for imaging metrics from this region to serve as valuable imaging biomarkers. However, most existing automated approaches for MTL segmentation do not incorporate anterior MTL subregions, and the few that do fail to account for its complex anatomical variability. Leveraging a unique postmortem dataset consisting of histology and structural MRI scans we aimed to develop an anatomically valid segmentation protocol for anterior entorhinal cortex (ERC), Brodmann Area (BA) 35, and BA36 and apply it for automated MTL segmentation of in vivo 3 tesla (T) MRI.