Basic Science and Pathogenesis.

Background: An imbalance between the production and clearance of amyloid beta (Aß) has emerged as a major cause of sporadic Alzheimer's disease (AD). Retinal wholemount studies can identify cell-specific involvement in Aß clearance mechanisms which cannot be accomplished in the brain ex vivo.

Methods: Eye cross-sections of double transgenic (Tg, APP-PS1) and non-carrier sibling female mice (n = 16, 4 per group) at 3- and 9- month ages were probed with antibodies 6E10 (Aβ1-16 amino-acid residues, soluble and insoluble species), ionized calcium-binding adapter molecule 1 (IBA1, microglia/macrophage), glial fibrillary acidic protein (GFAP, astrocytes), glutamine synthetase (GS, Müller cells) and aquaporin-4 (AQP4, membrane water channel) using immunofluorescence.

Basic Science and Pathogenesis.

Background: Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is a pathological process diagnosed at autopsy, involving deposition of TDP-43 in the medial temporal lobes. The name LATE-NC was recently proposed to represent the pathological process, while "LATE" has been suggested to represent the clinical syndrome. However, there are currently no available criteria to diagnose this syndrome during life, and the clinical phenotype is not well understood.

Basic Science and Pathogenesis.

Background: Autosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit thalamocortical hyperconnectivity that increases with age when they are presumably closer to symptom onset.

Clinical Manifestations.

Background: Frontotemporal dementia (FTD) presents with heterogeneous neuropsychiatric symptoms (NPS). These symptoms often begin prior to the onset of FTD, and progress throughout the prodromal stages of FTD. Particularly, familial FTD due to autosomal dominant genetic mutations might display mutation-specific NPS profiles.

Introspection about forced and free choice: Accurate subjective time estimation for externally as well as self-determined actions.

Free-choice behavior is unique in that actions are internally self-determined, unlike forced-choice behavior, which is externally specified. Several studies suggest these two action modes can lead to different behavioral, affective, and motivational outcomes. We examined whether people estimate free-choice differently from forced-choice processing time due to possible introspective biases associated with these modes.