Pick's Disease, Seeding an Answer to the Clinical Diagnosis Conundrum

Biomedicines. 2023 Jun 6;11(6):1646. doi: 10.3390/biomedicines11061646.

Abstract

Pick's disease (PiD) is a devastating neurodegenerative disease that is characterized by dementia, frontotemporal lobar degeneration, and the aggregation of 3R tau in pathognomonic inclusions known as Pick bodies. The term PiD has adopted many meanings since its conception in 1926, but it is currently used as a strictly neuropathological term, since PiD patients cannot be diagnosed during life. Due to its rarity, PiD remains significantly understudied, and subsequently, the etiology and pathomechanisms of the disease remain to be elucidated. The study of PiD and the preferential 3R tau accumulation that is unique to PiD is imperative in order to expand the current understanding of the disease and inform future studies and therapeutic development, since the lack of intervention strategies for tauopathies remains an unmet need. Yet, the lack of an antemortem diagnostic test for the disease has further complicated the study of PiD. The development of a clinical diagnostic assay for PiD will be a vital step in the study of the disease that will greatly contribute to therapeutic research, clinical trial design and patient recruitment and ultimately improve patient outcomes. Seed aggregation assays have shown great promise for becoming ante mortem clinical diagnostic tools for many proteinopathies, including tauopathies. Future research on adapting and optimizing current seed aggregation assays to successfully detect 3R tau pathogenic forms from PiD samples will be critical in establishing a 3R tau specific seed aggregation assay that can be used for clinical diagnosis and treatment evaluation.

Keywords: 3R tau; Pick’s disease; primary tauopathy; seed aggregation assays.

Publication types

  • Review

Grants and funding

O.A.R. is supported by NIH (RF1 NS085070; U01 NS100620; R01 AG056366; U19 AG071754; R01 NS078086), DOD (W81XWH-17-1-0249), The Michael J Fox Foundation, American Brain Foundation, and the Mayo Clinic LBD/Tau Center without Walls (U54-NS110435 & U54-NS100693). Mayo Clinic is an American Parkinson Disease Association (APDA) Mayo Clinic Information and Referral Center, an APDA Center for Advanced Research, and a Lewy Body Dementia Association (LBDA) Research Center of Excellence.