We used transmitochondrial cybrids that recapitulate pathogenic alterations observed in sporadic PD and AD patient brains and ASYN and Tau cellular models.
Immunoblot analyses of sarkosyl-insoluble tau from frozen brains showed an AD-type tau banding pattern with strong immunoreactivities. sTBI patients showed limited comorbidities, such as TDP-43, alpha-synuclein or AD pathology, whereas rTBI patients have high frequencies of them.
Messenger RNA (mRNA) transcripts [amyloid precursor protein (APP), α-synuclein (α-syn), Tau, neurofilament light gene (NF-L), DJ-1/PARK7, Fractalkine and Neurosin] and long non-coding RNAs (RP11-462G22.1 and PCA3) were differentially expressed in CSF exosomes in PD and AD patients.
Our findings demonstrated that SNCA contributes to LB pathology in AD patients, possibly via interaction with LRRK2, and suggested that expression regulation of these genes may be the molecular basis underlying the observed LB associations.