Evidence for a membrane lipid defect in Alzheimer disease.
We have previously shown that cells normally maintain their lipid metabolic pools at a critical composition, appropriate for spontaneous assembly of a stable membrane bilayer at their physiological temperature. When disease affects membrane lipids such that the new composition will only form a stable bilayer at a critical temperature (T*), which differs from the physiological value, membrane destabilization and hence cellular damage will necessarily ensue. We have previously tested this pathogenetic mechanism in metachromatic leukodystrophy, a disorder with a known primary lipid metabolic defect. In the present study, we found T* for cerebral cortex lipids from three Alzheimer disease (AD) patients ranged between 19 and 28 degrees C, independent of membrane protein composition. Control cortex lipids yielded a normal value for T* of 37 degrees C. Thus, one possible mechanism for neurodegeneration in AD is membrane destabilization secondary to a lipid compositional aberration, which shifts T* away from 37 degrees C. This lipid defect is brain region-specific as cerebellar lipids from the AD patients gave a normal value for T*. Studies aimed at delineating the nature of the biochemical anomaly are in progress.
Ginsberg
L
L
Laboratory of Physical Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
Atack
J R
JR
Rapoport
S I
SI
Gershfeld
N L
NL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D005260:Female; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013696:Temperature
D008051:Lipid Bilayers; D008563:Membrane Lipids