Distribution of big tau isoforms in the human central and peripheral nervous system

This project aims to characterize the distribution of “big tau,” a longer tau isoform expressed in the peripheral nervous system (PNS) and select central nervous system (CNS) regions, and to examine its relationship with aging and neurodegeneration. We performed mass spectrometric sequencing of big tau sequence and mapped its distribution across the human nervous system. Postmortem samples included brains from Alzheimer’s disease (AD), disease controls, and amyotrophic lateral sclerosis (ALS); spinal cord from young controls, disease controls and ALS; and peripheral nerves. Big and small tau levels were also quantified in the cerebrospinal fluid (CSF) from young normal controls, amyloid positive and amyloid negative participants. To reinforce the presence of big tau in the brain, iso-seq was performed on post-mortem brain tissue samples.