Laboratory of Neuropathology & Neuroscience, Grad Sch Pharm Sci, UTokyo

In FY2026, the Tomita Lab welcomes nine new members!

A new paper has been published!

The mechanism responsible for the production of APP669-711, a component of a blood biomarker that can detect senile plaques in the brains of patients with Alzheimer’s disease, has long remained unclear. In our previous study, we showed that ADAMTS4 contributes to approximately 40% of APP669-711 production, while the source of the remaining fraction was unknown. In this new study, we further investigated this question and found that ADAMTS5, an enzyme related to ADAMTS4, may also contribute to APP669-711 production.

This work was carried out in collaboration with Shimadzu Corporation. Congratulations to Miyabishara and Honoka!

Identification of ADAMTS5 as APP‐Cleaving Enzyme at the APP669 Site Alzheimer disease plasma biomarker APP669-711 is produced by two-step cleavage of amyloid precursor protein (APP) by APP669-cleaving enzymes and γ-secretase. In vitro, ADAMTS5 exhibits robust APP669-...

Congratulations to Daisuke, Maria, Ikumi (Ph.D.), Asahi, Kanata, Eishin (M.Sc.) for their degrees!

A new paper is out! We demonstrated that the compound M1, which controls the phagocytic activity of microglia via GPR34 signaling, can control the clearance of amyloid beta in Alzheimer disease. Congrats, Hayato and Sho!

Selective agonism of GPR34 stimulates microglial uptake and clearance of amyloid β fibrils - Alzheimer's Research & Therapy Background Microglia play a crucial role in brain homeostasis through phagocytosis of amyloid-β (Aβ) fibrils, a hallmark of Alzheimer disease (AD) pathology. The balance between Aβ production and clearance is critical for AD pathogenesis, with impaired clearance mechanisms potentially contributin...

Tomita lab started the 2025 fiscal year with 6 new members!!

Congratulations to Shiyori, Yuma, Chia Jen (Ph.D.), Aika, Chu Fan, Hiroto, Yoshiki, Tatsuya, Rie (M.Sc.) for their degrees!

A new paper is out! This is a paper that reveals the synaptogenic potential of the secreted form of Lingo2 from studies on animal models of autism. Congrats, Fumiaki and Ryota!

Soluble form of Lingo2, an autism spectrum disorder-associated molecule, functions as an excitatory synapse organizer in neurons - Translational Psychiatry Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impaired social communication and repetitive behaviors. In recent years, a pharmacological mouse model of ASD involving maternal administration of valproic acid (VPA) has become widely used. Newborn pups in this model show a...

Tomita Laboratory will start with 7 new members in FY2024!

Congratulations to Kyohei, Haruaki, Lejia, Hiroki, Kai (Ph.D.), Shuichirou, Mai, Honoka, Lisa, Hanako, Hikaru and Yung-Ning (M.Sc.) for successfully defending their thesis!

LRRK2, a protein that plays a major role in the pathogenesis of Parkinson disease, is known to phosphorylate a group of proteins called Rab family proteins Here we revealed that excessive phosphorylation of Rab12 causes abnormal subcellular localization of lysosomes, which are involved in the breakdown of proteins in cells. Various studies have strongly suggested that abnormal lysosome function is involved in the onset of Parkinson's. In addition, the relationship between the subcellular localization of lysosomes and their function is a topic that has been the focus of much attention. So our study suggests the pathological link between these mechanisms in the pathogenesis of PD. This is also a collaboration study with HACARUS Inc. Congrats, Kyohei, Miho and Genta!

Pathogenic LRRK2 compromises the subcellular distribution of lysosomes in a Rab12‐RILPL1‐dependent manner Mutations in LRRK2 cause familial Parkinson's disease. LRRK2 phosphorylates Rab12, which is accelerated by pathogenic mutations. We found that lysosomes clustered in a perinuclear region upon overexp...

Dysregulation of the TREM2 signaling pathway in microglia, responsible for brain immunity, has been shown to affect the risk of developing Alzheimer's; however, much remains unknown about the intracellular signaling mechanism of TREM2. In this study, we have shown that another Alzheimer's risk factor, INPP5D, functions in the TREM2 signaling pathway and is a key molecule linking amyloid-β to tau pathology. Congratulations, Akihiro and Sho!

INPP5D modulates TREM2 loss-of-function phenotypes in a β-amyloidosis mouse model The genetic associations of TREM2 loss-of-function variants with Alzheimer disease (AD) indicate the protective roles of microglia in AD pathogenesis.…