Alzheimer's disease through the eye of a mouse. Acceptance lecture for the 2001 Gayle A. Olson and Richard D. Olson prize.
There is now ample evidence that beta-amyloid proteins decrease memory. The SAMP8 mouse (P8) develops an early decline in the ability to learn and to retain new information. The studies reviewed here suggest that this is due to overproduction of beta-amyloid. Both antibodies to beta-amyloid and specific antisense to the amyloid precursor protein reverse these deficits in the P8 mouse. This antisense can cross the blood brain barrier. It is hypothesized that the overproduction of beta-amyloid leads to a decline in Delta(9) desaturase activity with an alteration in membrane fatty acids. This results in altered membrane mobility leading to a decline in neurotransmitter activity and a decreased release of acetylcholine. This decreased cholinergic activity results in a decreased ability of the P8 mouse to learn and retain new information.
Morley
John E
JE
Geriatric Research, Education, & Clinical Center (GRECC), VA Medical Center, St. Louis, MO, USA. morley@sluvca.slu.edu
Farr
Sue A
SA
Kumar
Vijaya B
VB
Banks
William A
WA
D000375:Aging / Q000187:drug effects / Q000502:physiology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001812:Blood-Brain Barrier; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D005227:Fatty Acids; D012739:Gonadal Steroid Hormones; D016376:Oligonucleotides, Antisense