MAPT and Alzheimer disease: Importantly, the current AT(N) framework overlooks the complexity of AD as reflected by the involvement of multiple biological pathways beyond amyloid and tau, including neuroinflammation, mitochondrial dysfunction, demyelination, axonal degeneration, synaptic loss and vascular changes, all of which contribute to the progressive cognitive decline in AD, likely with different degree of relevance across individuals (7, 8).