Neurotransmitter measures in the cerebrospinal fluid of patients with Alzheimer's disease: a review.
BACKGROUND
Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by progressive cognitive and functional decline, as well as by a variety of neuropsychiatric and psychological symptoms and behavioral dysfunctions. Various studies proposed the role of different neurotransmitter systems not only in AD-related cognitive, but also psychotic symptoms and behavioral and emotional deficits. Due to the close proximity, pathological neurochemical changes in brain occurring in AD are likely to be reflected in the cerebrospinal fluid (CSF). The purpose of this review is to provide a summary of the CSF neurotransmitter correlates of AD in order to get further insights into the potential role of altered neurotransmitters in the pathophysiology of AD and to offer novel AD biomarkers.


METHODS
PubMed and MEDLINE data bases were searched for English-language articles by using "Alzheimer's disease", "CSF" and "neurotransmitter" as primary terms. No time or article type constraints were applied. Moreover, the lists of references were searched manually for additional articles.


RESULTS
Changes in various correlates of cholinergic, monoaminergic and amino acid neurotransmitter systems, as well as neuropeptides, have been observed in CSF of AD patients. However, as the results of these studies have been controversial, the importance of CSF neurotransmitter parameters as potential biomarkers in AD remains quite unclear. The observed discrepancies could be bypassed by implementation of new sensitive methods, such as novel proteomics approaches that include protein separation techniques, mass spectroscopy and targeted multiplex panels of specific analytes.


CONCLUSIONS
Although no individual CSF neurotransmitter correlate was demonstrated as suitable biomarker of AD, a combined profile of several CSF neurochemical parameters might show enhanced sensitivity and specificity and thus contribute to earlier and more accurate diagnosis of AD, crucial for application of effective treatments.
Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka cesta 54, 10 000 Zagreb, Croatia, dsvob@irb.hr.
Dubravka Svob
DS
Strac
Dorotea
D
Muck-Seler
Nela
N
Pivac
D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism / Q000523:psychology; D001526:Behavioral Symptoms / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D042241:Early Diagnosis; D006801:Humans; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid / Q000145:classification; D012680:Sensitivity and Specificity
D015415:Biomarkers; D018377:Neurotransmitter Agents