Impact of aging: sporadic, and genetic risk factors on vulnerability to apoptosis in Alzheimer's disease.
The identification of specific genetic (presenilin-1 [PS1] and amyloid precursor protein [APP] mutations) and environmental factors responsible for Alzheimer's disease (AD) has revealed evidence for a shared pathway of neuronal death. Moreover, AD-specific cell defects may be observed in many other nonneuronal cells (e.g., lymphocytes). Thus, lymphocytes may serve as a cellular system in which to study risk factors of sporadic, as well as genetic AD in vivo. The aim of our present study was to clarify whether lymphocytes bearing genetic or sporadic risk factors of AD share an increased susceptibility to cell death. Additionally we examined whether a cell typespecific vulnerability pattern was present and how normal aging, the main risk factor of sporadic AD, contributes to changes in susceptibility to cell death. Here, we report that lymphocytes affected by sporadic or genetic APP and PS1 AD risk factors share an increased vulnerability to cell death and exhibit a similar cell type-specific pattern, given that enhanced vulnerability was most strongly developed in the CD4+ T-cell subtype. In this paradigm, sporadic risk factors revealed the highest impact on cell type-specific sensitivity of CD4+ T cells to apoptosis. In contrast, normal aging results in an increased susceptibility to apoptosis of both, CD4+ and CD8+ T cells.
Schindowski
Katharina
K
Department of Pharmacology, Biocenter, J.W. Goethe University of Frankfurt, Marie-Curie-Str. 9, D-60439 Frankfurt am Main, Germany.
Kratzsch
Tilmann
T
Peters
Jürgen
J
Steiner
Barbara
B
Leutner
Silke
S
Touchet
Natalie
N
Maurer
Konrad
K
Czech
Christian
C
Pradier
Laurent
L
Frölich
Lutz
L
Müller
Walter E
WE
Eckert
Anne
A
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000172:deficiency / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002452:Cell Count; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D053764:Presenilin-1; D012016:Reference Values; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D017252:CD3 Complex; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1