Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture.
The neurodegeneration and amyloid deposition of sporadic Alzheimer disease (AD) also occur in familial AD and in all trisomy-21 Down syndrome (DS) patients, suggesting a common pathogenetic mechanism. We investigated whether defective processing of damaged DNA might be that mechanism, as postulated for the neurodegeneration in xeroderma pigmentosum, a disease with defective repair not only of UV radiation-induced, but also of some oxygen free radical-induced, DNA lesions. We irradiated AD and DS skin fibroblasts or blood lymphocytes with fluorescent light, which is known to cause free radical-induced DNA damage. The cells were then treated with either beta-cytosine arabinoside (araC) or caffeine, and chromatid breaks were quantified. At least 28 of 31 normal donors and 10 of 11 donors with nonamyloid neurodegenerations gave normal test results. All 12 DS, 11 sporadic AD, and 16 familial AD patients tested had abnormal araC and caffeine tests, as did XP-A cells. In one of our four AD families, an abnormal caffeine test was found in all 10 afflicted individuals (including 3 asymptomatic when their skin biopsies were obtained) and in 8 of 11 offspring at a 50% risk for AD. Our tests could prove useful in predicting inheritance of familial AD and in supporting, or rendering unlikely, the diagnosis of sporadic AD in patients suspected of having the disease.
Parshad
R P
RP
Department of Pathology, Howard University College of Medicine, Washington, DC 20059, USA.
Sanford
K K
KK
Price
F M
FM
Melnick
L K
LK
Nee
L E
LE
Schapiro
M B
MB
Tarone
R E
RE
Robbins
J H
JH
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics; D002110:Caffeine / Q000494:pharmacology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002842:Chromatids / Q000187:drug effects / Q000528:radiation effects*; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004314:Down Syndrome / Q000235:genetics; D005260:Female; D005347:Fibroblasts; D016193:G1 Phase; D016195:G2 Phase; D006801:Humans; D008027:Light / Q000009:adverse effects*; D008214:Lymphocytes; D008297:Male; D014466:Ultraviolet Rays / Q000009:adverse effects
D003561:Cytarabine; D002110:Caffeine; D004247:DNA