Cerebrospinal fluid beta-glucocerebrosidase activity is reduced in Dementia with Lewy Bodies.
The autophagy-lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of beta-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). We recently found a decreased activity of lysosomal hydrolases, namely beta-glucocerebrosidase, in cerebrospinal fluid of PD patients. We have thus measured the activity of these enzymes - alpha-mannosidase (EC 3.2.1.24), beta-mannosidase (EC 3.2.1.25), beta-glucocerebrosidase (EC 3.2.1.45), beta-galactosidase (EC 3.2.1.23) and beta-hexosaminidase (EC 3.2.1.52) - in cerebrospinal fluid of patients suffering from DLB, Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and controls. Alpha-mannosidase activity showed a marked decrease across all the pathological groups as compared to controls. Conversely, beta-glucocerebrosidase activity was selectively reduced in DLB, further suggesting that this enzyme might specifically be impaired in synucleinopathies.
Parnetti
L
L
Section of Neurology, University of Perugia, Italy. parnetti@unipg.it
Balducci
C
C
Pierguidi
L
L
De Carlo
C
C
Peducci
M
M
D'Amore
C
C
Padiglioni
C
C
Mastrocola
S
S
Persichetti
E
E
Paciotti
S
S
Bellomo
G
G
Tambasco
N
N
Rossi
A
A
Beccari
T
T
Calabresi
P
P
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000201:enzymology; D003704:Dementia / Q000134:cerebrospinal fluid / Q000201:enzymology; D005260:Female; D005962:Glucosylceramidase / Q000134:cerebrospinal fluid*; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid* / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D043323:alpha-Mannosidase / Q000134:cerebrospinal fluid; D001616:beta-Galactosidase / Q000134:cerebrospinal fluid; D044902:beta-Mannosidase / Q000134:cerebrospinal fluid; D001619:beta-N-Acetylhexosaminidases / Q000134:cerebrospinal fluid
D001616:beta-Galactosidase; D043323:alpha-Mannosidase; D044902:beta-Mannosidase; D005962:Glucosylceramidase; D001619:beta-N-Acetylhexosaminidases