Early Alzheimer's Disease with frequent neuritic plaques harbors neocortical tau seeds distinct from primary age-related tauopathy.

Tau neurofibrillary tangles (NFTs) in the presence of amyloid-β (Aβ) plaques are required for the diagnosis of Alzheimer's Disease (AD) and closely track with cognitive impairment, yet cognitively normal aged individuals frequently exhibit NFTs arising from tau seed accumulation. This may suggest that not all tau species are equally pathogenic and raises the question of whether unidentified tau modifications augment tau seeding activity and neurodegeneration in AD. We investigated how biochemical modifications of tau relate to clinicopathological outcomes in a cohort of 38 patients with Braak-matched AD neuropathologic change (ADNC) or primary age-related tauopathy (PART), a 3R/4R tauopathy with identical tau filament core structure to ADNC but with little to no Aβ deposition.

Structure of Galectin-3 bound to a model membrane containing ganglioside GM1.

Galectin-3 (Gal-3) is a β-galactosidase-binding protein involved in various biological processes, including neuronal growth and adhesion. The pairing of Gal-3 with ganglioside GM1's pentasaccharide chain at the outer leaflet of the plasma membrane, which triggers downstream cell-signaling cascades, seems to be involved in these processes. A crucial feature of Gal-3 is its ability to form oligomers and supramolecular assemblies that connect various carbohydrate-decorated molecules.