title: Progressive decline of glucocerebrosidase in aging and Parkinson's disease.
abstract: The principal risk factor for developing most adult onset neurodegenerative diseases is aging, with incidence rising significantly after age 50. Despite research efforts, the causes of Parkinson's disease (PD) remain unknown. As neurons age, they show signs of diminished lysosomal and mitochondrial function, including increased oxidative stress and accumulation of misfolded proteins, and these changes become exacerbated PD. We show that activity of the lysosomal hydrolase glucocerebrosidase gradually diminishes with age in the substantia nigra and putamen of healthy controls. This reduction is comparable to glucocerebrosidase activity in GBA1-mutation carrier PD patients. These data, demonstrate for the first time that an age-dependent reduction in glucocerebrosidase activity may lower the threshold for developing PD.
authors.affiliation: Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital Belmont, Massachusetts, 02478.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Rocha
authors.affiliation: Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital Belmont, Massachusetts, 02478.
authors.forename: Gaynor A
authors.initials: GA
authors.lastname: Smith
authors.affiliation: Shire 300 Shire Way, Lexington, Massachusetts, 02421.
authors.forename: Eric
authors.initials: E
authors.lastname: Park
authors.affiliation: Shire 300 Shire Way, Lexington, Massachusetts, 02421.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Cao
authors.affiliation: Shire 300 Shire Way, Lexington, Massachusetts, 02421.
authors.forename: Eilish
authors.initials: E
authors.lastname: Brown
authors.affiliation: Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital Belmont, Massachusetts, 02478.
authors.forename: Penelope
authors.initials: P
authors.lastname: Hallett
authors.affiliation: Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital Belmont, Massachusetts, 02478.
authors.forename: Ole
authors.initials: O
authors.lastname: Isacson