Shared perturbations in the metallome and metabolome of Alzheimer’s, Parkinson’s, Huntington’s, and dementia with Lewy bodies: A systematic review

Despite differences in presentation, age-related dementing diseases such as Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s diseases (HD), and dementia with Lewy bodies (DLB) may share pathogenic processes. This review aims to systematically assemble and compare findings in various biochemical pathways across these four dementias. PubMed and Google Scholar were screened for articles reporting on brain and biofluid measurements of metals and/or metabolites in AD, PD, HD, or DLB. Articles were assessed using specific a priori-defined inclusion and exclusion criteria. Of 284 papers identified, 198 met criteria for inclusion. Although varying coverage levels of metals and metabolites across diseases and tissues made comparison of many analytes impossible, several common findings were identified: elevated glucose in both brain tissue and biofluids of AD, PD, and HD cases; increased iron and decreased copper in AD, PD and HD brain tissue; and decreased uric acid in biofluids of AD and PD cases. Other analytes were found to differ between diseases or were otherwise not covered across all conditions. These findings indicate that disturbances in glucose and purine pathways may be common to AD, PD, and HD. However, standardisation of methodologies and better coverage in some areas – notably of DLB – are necessary to validate and extend these findings.