Age-dependent decline of neprilysin in Alzheimer's disease and normal brain: inverse correlation with A beta levels.
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.
Hellström-Lindahl
E
E
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
Ravid
R
R
Nordberg
A
A
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism*; D011180:Postmortem Changes; D013223:Statistics as Topic; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D015260:Neprilysin