Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

Age-dependent decline of neprilysin in Alzheimer's disease and normal brain: inverse correlation with A beta levels.

Hellström-Lindahl E, Ravid R, Nordberg A

Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Division of Molecular Neuropharmacology, Geriatric-lab, Novum, Floor 4, S-141 86 Stockholm, Sweden. ewa.hellstrom-lindahl@ki.se

Brain deposition of amyloid-beta (A beta) is a pathological hallmark of Alzheimer disease (AD) but A beta is also detected in non-demented elderly individuals. Neprilysin has been shown to be an important enzyme to degrade A beta in brain. We investigated whether decreased neprilysin levels contributes to the accumulation of A beta in AD and in normal aging. No difference in neprilysin protein and mRNA levels were found between AD subjects and age-matched controls. Protein levels of neprilysin were reduced with age in the temporal and frontal cortex of AD and normal brain. A significant positive correlation between insoluble A beta 40 and A beta 42 with age was found in cortex of normal brain whereas in AD brain the correlation between age and A beta was weaker. Our findings of an inverse correlation between neprilysin and insoluble A beta levels in both groups suggest that neprilysin is involved in the clearance of A beta. The observed age-dependent decline in neprilysin may be related to the increased A beta levels during normal aging. The similar rate of decline in neprilysin with age may not be the major cause of the high levels of A beta associated with AD but is likely to be a trigger of AD pathology.

Published 7 January 2008 in Neurobiol Aging, 29(2): 210-21.
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