Naoto Watamura

This paper develops a scalable human neuronal model of 4R tauopathy with endogenous seed-competent tau for drug discovery.

This study uses mouse models with tau mutations to show two distinct pathogenic mechanisms in tauopathies, with different progression patterns and responses to amyloid.

The paper describes the development of triple MAPT mutation knock-in mice that exhibit early tau pathology and behavioral abnormalities, useful for studying frontotemporal dementia and related tauopathies.

This paper investigates the metabolic stability and deposition of A{beta}3pE-42, a target of the Alzheimer's antibody donanemab, showing it is more stable than other A{beta}X-42 species and accumulates with age.

This study compares the roles of NEP and IDE in Aβ metabolism using double knockout mice, finding NEP primarily degrades insoluble Aβ and its deficiency contributes to AD pathology.

This study develops App knock-in mice without Swedish mutations to investigate β-secretase inhibition and endosomal abnormalities in Alzheimer's disease.

This paper introduces a new mouse model that accumulates wild-type human Aβ rapidly, showing more severe cored plaque pathology and neuroinflammation than existing models.

This study identifies α-endosulfine as a negative regulator of neprilysin activity, showing that its deficiency reduces amyloid β42 deposition in Alzheimer's disease models.

This study identifies SST1 and SST4 as redundant regulators of neprilysin, a key amyloid beta-degrading enzyme, and shows that targeting these receptors reduces Aβ pathology and improves cognition in an AD mouse model.