Basic Science and Pathogenesis.

Background: Previously, the Penn Frontotemporal Degeneration (FTD) Center developed and validated criteria to stratify pedigrees of patients with FTD by likelihood of identifying a genetic etiology (Wood, JAMA Neurol., 2013). Pedigrees were classified as high-risk, medium-risk, low-risk, apparent sporadic, or unknown significance.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease, and it is characterized by aggregation of misfolded proteins in the brain. Intraneuronal accumulation of tau pathology form neurofibrillary tangles (NFT) in AD. The assessment of the severity of intraneuronal inclusions holds significance in studying the clinicopathological associations in neurodegenerative diseases.

Basic Science and Pathogenesis.

Background: We recently found region-specific patterns of iron-rich gliosis in frontotemporal lobar degeneration (FTLD) groups with tau (FTLD-Tau; PSP) and TDP-43 (FTLD-TDP) pathology using iron-sensitive MRI of whole-hemispheres. These patterns largely corresponded to regions of early pathology reported in previous traditional histopathologic staging schemes of protein inclusions for FTLD-Tau and FTLD-TDP. Ferritin light chain (FLC) reactivity highlights activated glia but has not been studied extensively in FTLD.

Basic Science and Pathogenesis.

Background: Transcriptomic and pathological studies indicate that microglia play a key role in the progression of Alzheimer's disease (AD). Throughout the stages of the AD continuum, there may be varying microglia phenotypes, such as the disease-associated microglia (DAM). Microglia proteins have been detected in cerebrospinal-fluid (CSF), providing a quantifiable avenue for potential stage-detection.

Basic Science and Pathogenesis.

Background: Limbic predominant age-related TDP-43 encephalopathy (LATE) is a common co-pathology in Alzheimer's disease (AD) and is associated with advanced cognitive impairment and severe atrophy in limbic regions. In AD, various maturation stages for tau neurofibrillary tangles have been characterized and can be selectively marked by monoclonal tau antibodies, providing insight into disease progression. Indeed, AD tau pathology progresses from an early "paperclip" conformation, marked by the MC1 epitope to a C-terminally truncated form of tau, marked by MN423 epitope.