Amyloid-β and τ biomarkers in Parkinson's disease–dementia

Abstract

Dementia is a frequent and devastating non-motor complication of advanced Parkinson's disease (PD). There is growing evidence of a synergistic role of Alzheimer's-type brain lesions containing τ and amyloid-β (Aβ) proteins and cortical Lewy aggregates in PD-related dementia (PDD). Therefore, biomarkers of both τ and Aβ may be seen as diagnostic and predictive markers of PDD. Here, we review the available studies in PD and PDD using cerebrospinal fluid (CSF) total τ, phospho-τ, and/or Aβ levels, and PET probes targeting Alzheimer's-type lesions. Overall, high CSF τ and phospho-τ levels and/or low CSF Aβ levels have been found in part of PDD patients, and a longitudinal study has found greater worsening in cognitive performance over time in non-demented PD patients with low baseline CSF Aβ levels. Few studies are available on the use of PET imaging in PD, all of them using the Pittsburgh B compound (PIB), and with figures of about 30% of scans with PIB uptake in the AD-range in PDD. We conclude that these CSF and PET markers deserve further evaluation as candidate biomarkers of dementia in PD. According to this, we are currently undertaking a longitudinal project on the predictive value of dementia of the combined use of CSF τ and Aβ and 18F-FDDNP PET in PD.