Years before plaques develop in AD, the cingulate cortex brims with excess activity. Ditto in APP knock-in mice, where listless astrocytes allow a neuronal frenzy. Do astrocytes play into the pathological cascade this early?
In neurons lacking PS1, late endosomes get bogged down by imbalanced calcium. This puts kinases in a tizzy, slows motor proteins, and makes neurites dystrophic.
Depleted of cholesterol, neurons laid out the welcome mat for tau aggregates, which readily crossed into the cytosol and seeded aggregation there. Adding cholesterol blocked entry and seeding.
The guidance may help sponsors increase racial diversity in clinical trials. Studies in U.S. veterans and other cohorts show differences in incidence, and in blood levels of tau by race.
Excitatory neurons from people who died with Alzheimer’s disease carried more mutations than did neurons from healthy controls. Do such variants contribute to the demise of neurons?
Interactions with both remote and local amyloid-laden neurons drive tangles through the Alzheimer's brain. Is person-to-person variability in these interactions why patients differ in their progression?
In its national coverage determination, Medicare limits Aduhelm coverage to clinical trials, but OKs registry-based studies for traditionally approved anti-Aβ antibodies. This may change once new efficacy data comes out.
Low levels of Aβ37, 38, 40 reflect low processive activity of γ-secretase. They track with age at onset in people with autosomal-dominant mutations, and may track with cognitive decline in sporadic AD.
Applied to more than 500 alleles in APP, PSEN1, and PSEN2, the new classification can help scientists gauge how pathogenic, or benign, a given variant might be
In a game changer for the field, three papers report similar structures for TMEM106b fibrils. One claims they comprise the lion’s share of TDP-43 aggregates.
In the field's quest for disease-modifying treatments, two different α-synuclein vaccines and two antibodies look promising in preclinical studies, as well.