Neuropathology-based approach reveals novel Alzheimer's Disease genes and highlights female-specific pathways and causal links to disrupted lipid metabolism: insights into a vicious cycle.

Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.

Site-specific seeding of Lewy pathology induces distinct pre-motor cellular and dendritic vulnerabilities in the cortex.

Circuit-based biomarkers distinguishing the gradual progression of Lewy pathology across synucleinopathies remain unknown. Here, we show that seeding of α-synuclein preformed fibrils in mouse dorsal striatum and motor cortex leads to distinct prodromal-phase cortical dysfunction across months. Our findings reveal that while both seeding sites had increased cortical pathology and hyperexcitability, distinct differences in electrophysiological and cellular ensemble patterns were crucial in distinguishing pathology spread between the two seeding sites.

Social context modulates active avoidance: Contributions of the anterior cingulate cortex in male and female rats.

Actively avoiding danger is necessary for survival. Most research on active avoidance has focused on the behavioral and neurobiological processes when individuals learn to avoid alone, within a solitary context. Therefore, little is known about how social context affects active avoidance.

Do biopsychosocial factors predict the level of physical activity in individuals with persistent shoulder pain?

Objective: The objective of this cross-sectional study was to compare the physical activity level between individuals with and without rotator cuff related shoulder pain (RCRSP), and, in individuals with RCRSP, investigate whether biopsychosocial factors are associated with the physical activity level.

Methods: Seventy-four participants with and 84 participants without RCRSP wore a fitness tracking watch for seven consecutive days to assess physical activity (step count, moderate-to-vigorous physical activity (MVPA)-minutes). Additionally, participants with RCRSP completed questionnaires on their level of pain, disability, and physical activity (short version of the International Physical Activity Questionnaire [IPAQ]), as well as on biopsychosocial factors, including resilience, stress, catastrophizing, anxiety and depressive symptoms, self-efficacy, and social support.