Mini Review
Volume 13 Issue 6 - 2021
TRAPPC6A△ is a Potential Marker for the Progression of Alzheimer’s Disease from Middle Age
Nan-Shan Chang1,2,3*
1Institute of Molecular Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
2Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
3Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan, ROC
*Corresponding Author: Nan-Shan Chang, Institute of Molecular Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Received: May 11, 2021; Published: May 25, 2021


Alteration of trafficking protein particle (TRAPP) family proteins has been implicated in the pathogenesis for neurodegeneration. For example, a missense mutation in TRAPPC6A gene could cause protein accumulation in patients with a neurodevelopmental syndrome and dysmorphic features. TRAPPC6AD (or TPC6AΔ) is an N-terminal internal-deletion isoform of intracellular TRAPPC6A protein. TPC6AΔ aggregates, with Ser35 phosphorylation, can be found in the hippocampus and cortex of middle-aged postmortem normal humans, whereas amyloid beta (Aβ) is barely detectable. Downregulation of WWOX (WW domain-containing oxidoreductase) in the brain progressively induces TPC6AΔ aggregate formation and the aggregates serve as seeding posts for the subsequent aggregation of TIAF1 (TGF-β-induced antiapoptotic factor) and SH3GLB2 (SH3 domain-containing GRB2 like, endophilin B2), followed by caspase activation and ultimately generation of amyloid β plaques and tau tangles. Overall, pathogenic TPC6AD is an extracellular matrix protein that forms aggregates in the hippocampus and cortex of middle-aged healthy individual. If both wild type TPC6A and TPC6AD are present in the blood circulation, the ratios of TPC6AD/TPC6A protein can be regarded as a potential index for AD progression from middle age.

Keywords: TRAPPC6A; TRAPPC6AD; TIAF1; SH3GLB2; WWOX; Neurodegeneration; Alzheimer’s Disease


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Citation: Nan-Shan Chang. “TRAPPC6A△ is a Potential Marker for the Progression of Alzheimer’s Disease from Middle Age”. EC Neurology 13.6 (2021): 23-27.

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