Evaluation of cholinergic markers in Alzheimer's disease and in a model of cholinergic deficit.
Cognitive deficits in neuropsychiatric disorders, such as Alzheimer's disease (AD), have been closely related to cholinergic deficits. We have compared different markers of cholinergic function to assess the best biomarker of cognitive deficits associated to cholinergic hypoactivity. In post-mortem frontal cortex from AD patients, acetylcholine (ACh) levels, cholinacetyltransferase (ChAT) and acetylcholinesterase (AChE) activity were all reduced compared to controls. Both ChAT and AChE activity showed a significant correlation with cognitive deficits. In the frontal cortex of rats with a selective cholinergic lesion, all cholinergic parameters measured (ACh levels, ChAT and AChE activities, "in vitro" and "in vivo" basal ACh release) were significantly reduced. AChE activity was associated to ChAT activity, and even more, to "in vivo" and "in vitro" basal ACh release. Quantification of AChE activity is performed by an easy and cheap method and therefore, these results suggest that determination of AChE activity may be used as an effective first step method to evaluate cholinergic deficits.
Gil-Bea
Francisco Javier
FJ
Laboratory of Neuropharmacology, Department Pharmacology, School of Medicine, Center for Applied Medical Research (CIMA), University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
García-Alloza
Mónica
M
Domínguez
Jon
J
Marcos
Beatriz
B
Ramírez
María Javier
MJ
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D000922:Immunotoxins; D008297:Male; D008609:Mental Status Schedule; D009699:N-Glycosyl Hydrolases; D011180:Postmortem Changes; D051381:Rats; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013223:Statistics as Topic; D013429:Sulfatases / Q000378:metabolism*; D013997:Time Factors
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D000110:Acetylcholinesterase; D013429:Sulfatases; C019889:choline-sulfatase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine