Correlations between Alzheimer's Disease Cerebrospinal Fluid Biomarkers and Cerebral Glucose Metabolism after 12 Months of Phenserine Treatment

• New therapeutic strategies in Alzheimer's disease (AD) are focused on targeting amyloid-beta (A beta) to modify the underlying cause of the disease rather than just the symptoms. The aim of this study was to investigate the long-term effects of treatment with the anti-A beta compound phenserine on (i) cerebrospinal fluid (CSF) biomarkers for A beta and tau pathology and (ii) brain metabolism as assessed by the regional cerebral metabolic rate for glucose (rCMRglc), using positron emission tomography. Twenty patients with mild AD were included in the study and after 12 months treatment with phenserine, CSF A beta(40) and alpha- and beta-secretase-cleaved soluble amyloid-beta protein precursor (sA beta PP) levels had significantly increased and rCMRglc had stabilized. Levels of CSF A beta(40) and sA beta PP correlated positively with rCMRglc and cognition while CSF A beta(42) levels, the A beta(42/40) ratio, P-tau, and T-tau correlated negatively with rCMRglc and cognition. In summary, long-term phenserine treatment resulted in increased levels of CSF A beta(40), sA beta PP alpha, and sA beta PP beta, which positively correlated with improvements in rCMRglc and cognition. The study illustrates the value of using biomarkers in the CSF and brain for evaluation of drug effects.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

Alzheimer's disease

cerebral glucose metabolism

cerebrospinal fluid

phenserine

positron emission

MILD COGNITIVE IMPAIRMENT

AMYLOID PRECURSOR PROTEIN

LONGITUDINAL PET

EVALUATION

DRUG-DEVELOPMENT

CSF BIOMARKERS

A-BETA

CLINICAL-TRIALS

TRANSGENIC MICE

EARLY-DIAGNOSIS

DOUBLE-BLIND

Neurosciences

Alzheimer's disease

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