INVESTIGADORES
CASTAÑO Eduardo Miguel
artículos
Título:
Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer?s disease
Autor/es:
KALBACK WM; ESH CL; CASTAÑO EM; RAHMAN A; KOKJOHN T,; LUEHRS DC; SUE LI; CISNEROS R; GERBER F; RICHARDSON C; BOHRMANN B; BEACH TG; ROHER AE
Revista:
NEUROLOGICAL RESEARCH.
Editorial:
MANEY PUBLISHING
Referencias:
Lugar: London; Año: 2004 vol. 26 p. 525 - 539
ISSN:
0161-6412
Resumen:
We postulate that severe atherosclerotic occlusion of the circle of
Willis and leptomeningeal arteries is an important factor in the
pathogenesis of some sporadic Alzheimer's disease (AD) cases. These
arterial stenoses are complicated by an overwhelming amyloid
accumulation in the walls of leptomeningeal and cortical arteries
resulting in a significant decrease in perfusion pressure and consequent
ischemia/hypoxia of the brain tissue. We also propose that the distal
areas of the white matter (WM) will be the first affected by a lack of
oxygen and nutrients. Our hypotheses are supported by the following
observations: (1) the number of stenoses is more frequent in AD than in
the control population (p = 0.008); (2) the average index of occlusion
is greater in AD than in the control group (p < 0.00001); (3) the
index of stenosis and the total number of stenoses per case are
positively correlated (R = 0.67); (4) the index of stenosis correlates
with the neuropathological lesions of AD and with the MMSE psychometric
test; (5) the number and degree of atherosclerosis of the anterior,
middle and posterior cerebral arteries is more severe in cases of AD
than in the control population; (6) atherosclerosis severity is
apparently associated with the severity of the vascular amyloidosis; (7)
the WM rarefaction correlates with the severity of the atherosclerosis
and vascular amyloidosis; (8) the total cell count and microvessel count
in the areas of WM rarefaction correlate with the neuropathological
lesions of AD and with the MMSE score. Our data strongly suggest that
severe hemodynamic disturbances contribute to sporadic AD and support
the numerous observations indicating cardiovascular system participation
in the pathogenesis of these dementias.