Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity

Annals of Neurology - Tập 27 Số 5 - Trang 457-464 - 1990
Steven T. DeKosky1, Stephen W. Scheff1
1Departments of Neurology, and Anatomy and Neurobiology, and Sanders Brown Center on Aging, Lexington Veterans Administration and University of Kentucky Medical Centers, Lexington, KY

Tóm tắt

AbstractUltrastructural studies of biopsied cortical tissue from the right frontal lobe of 8 patients with mild to moderate Alzheimer's disease (AD) revealed that the number of synapses in lamina III of Brodmann's area 9 was significantly decreased when compared with the number in age‐matched control brains (n = 9; postmortem time, < 13 hours). Further decline in synaptic number was seen in age‐matched autopsied AD specimens. In the AD brains there was significant enlargement of the mean apposition length, which correlated with degree of synapse loss; as synapse density declined, synapse size increased. The enlargement of synapses, coupled with the decrease in synaptic number, allowed the total synaptic contact area per unit volume to remain stable in the patients who underwent biopsy. In autopsied subjects who had AD, there was no further enlargement of mean synaptic contact area. There was a significant correlation between synapse counts and scores on the Mini‐Mental State examination in the patients who underwent biopsy. Lower mental status scores were associated with greater loss of synapses. Choline acetyltransferase activity was significantly decreased in the biopsied group and declined further in the autopsied specimens of AD. There was no relationship between choline acetyltransferase activity and scores on the Mini‐Mental State examination or synapse number. There is evidence of neural plasticity in the AD neuropil; synaptic contact size increased in patients who had biopsy and possibly compensated for the numerical loss of synapses. But by end stage of the disease, the ability of the cortex to compensate was exceeded and both synapse number and synaptic contact area declined. The loss of neuronal connectivity, indexed by loss of synapses, predicted the degree of cognitive impairment in the patients who underwent biopsy and indicated a degree of structural change in AD brain not likely to be affected by pharmacotherapy.

Từ khóa


Tài liệu tham khảo

10.1126/science.7046051

10.1038/288279a0

10.1056/NEJM198604103141506

DeKosky ST, 1985, Handbook of neurochemistry, 617

10.1056/NEJM198906013202209

10.1002/ana.410100209

10.1007/BF00687457

10.1126/science.7058341

10.1212/WNL.32.2.164

10.1136/jnnp.51.6.842

10.1007/BF00692056

10.1126/science.6474172

10.1212/WNL.32.11.1227

10.1126/science.493989

10.1016/0197-4580(90)90059-9

Davies P, 1982, Biological aspects of Alzheimer's disease, 255

10.1136/jnnp.49.3.229

10.1111/j.1471-4159.1983.tb11311.x

10.1016/0022-510X(82)90026-0

Thal LJ, 1988, Current research in Alzheimer therapy, 103

10.1056/NEJM198611133152001

Stern Y, 1987, Effects of oral physostigmine on Alzheimer's disease, Neurology, 37, 306

10.3928/0048-5713-19870301-09

10.3171/jns.1989.71.4.0481

10.1016/0022-510X(87)90057-8

10.1007/BF00684929

10.1111/j.1600-0404.1986.tb03533.x

10.1212/WNL.39.3.355

10.1007/BF01245030

10.1016/0304-3940(89)90582-X

Harbaugh RE, 1985, Brain biopsy in Alzheimer's disease: surgical technique and indications, Bull Clin Neurosci, 50, 39

10.1212/WNL.34.7.939

10.1176/ajp.139.9.1136

10.1001/archneur.1985.04060100083029

10.1002/cne.902310205

10.1111/j.1471-4159.1975.tb11895.x

Ellman GL, 1961, A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem Pharmacol, 10, 88, 10.1016/0006-2952(61)90145-9

10.1016/S0021-9258(19)52451-6

Winer BJ, 1971, Statistical principles in experimental design

10.1016/0022-3956(75)90026-6

10.1111/j.1365-2990.1988.tb00880.x

Hillman DE, 1985, Synaptic plasticity, 39

10.1126/science.4071042

10.1016/0006-8993(88)90706-8

10.1111/j.1471-4159.1982.tb04695.x

Thông tin
Thông tin xuất bản

Annals of Neurology

Tập 27 Số 5

457-464

Thông tin tác giả