Pathological data from autopsies genotyped for PD-related mutations in alpha-synuclein, Parkin, PINK1, DJ1, LRRK2 and glucocerebrosidase have accumulated in recent years. The aim of this review is to systematically review all pathological reports of mutation carriers and to identify pathological patterns and gaps in the currently available data.

A systematic review of the English literature using the terms “Parkinson’s disease”, “brain pathology”, “autopsy”, and the specific gene nomenclature, and any combination of the above.

Most studies included reports of convenience samples, either cases that were pre-identified as mutation carriers before autopsy, or screens of Lewy body brain banks. Nineteen autopsies of alpha-synuclein mutation carriers, 49 of LRRK2 mutation carriers, 9 of Parkin mutation carriers, one of PINK1 mutation carrier and 90 of glucocerebrosidase mutation carriers were identified. Most autopsies of alpha-synuclein, LRRK2 G2019S and glucocerebrosidase mutation carriers demonstrated Lewy body pathology as opposed to Parkin and LRRK2 non-G2019S mutation carriers. However, there was a marked variability in pathological findings even among carriers of identical mutations. Pathological data from DJ1 mutation carriers, non-manifesting mutation carriers (e.g., of LRRK2 mutations), and carriers of a single Parkin mutation were lacking.

In gathering together all studies of PD autopsies with an identified genetic risk, this review highlights the wealth of information generated, as well as shortcomings in the available data. In particular, there is a need for larger, unbiased pathological studies. Differential association of Lewy pathology with specific mutations may reflect heterogeneity in pathogenic mechanisms among the different PD-related genes.