Re-evaluation of the structural organization of neuritic plaques in Alzheimer's disease.
We re-examined the relationship among synaptic pathology, subcellular abnormalities within neurites in the plaques and beta-amyloid deposits of Alzheimer's disease (AD) using laser confocal imaging and computer-aided serial section reconstruction techniques. Analysis of serial optical sections of neuritic plaques double-immunolabeled for anti-beta-amyloid/anti-tau-2 revealed that 35% of this type of plaque contained a dense amyloid core with clusters of peripheral abnormal neurites. The other 65% were without a dense core and were mainly composed of abundant abnormal neuritic clusters with bundles of amyloid distributed throughout the neuritic plaque. While two-dimensional (2-D) analysis of the plaques has suggested that neurites are distributed in the plaque periphery with beta-amyloid localized in its center, serial section analysis showed the opposite arrangement can also be true. Three-dimensional (3-D) reconstructions of serial optical sections showed that the tau-positive tortuous axons clustered in the neuritic plaques were often continuous with synaptophysin-positive distended terminals. Analysis of electron micrographs from serial sections showed continuity among the different segments of the neurites. Further analysis of the computer generated 3-D reconstructed neuritic plaques (both from serial electron micrographs and serial optical sections), viewed as continuous rotating loops, confirmed that a great majority of the plaque volume was occupied by the clustered and continuous abnormal neurites, while the amyloid fibrils were compressed and displaced to the periphery of the plaque. The 3-D imaging of the neuritic plaques in AD suggests a more widespread and active neuritic damage than that predicted from 2-D observations.(ABSTRACT TRUNCATED AT 250 WORDS)
Masliah
E
E
Department of Neurosciences, University of California, San Diego, La Jolla 92093-0624.
Mallory
M
M
Deerinck
T
T
DeTeresa
R
R
Lamont
S
S
Miller
A
A
Terry
R D
RD
Carragher
B
B
Ellisman
M
M
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D002540:Cerebral Cortex / Q000737:chemistry / Q000473:pathology*; D003936:Diagnosis, Computer-Assisted; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D016501:Neurites / Q000737:chemistry / Q000473:pathology*; D013569:Synapses / Q000737:chemistry / Q000473:pathology; D016708:Synaptophysin / Q000032:analysis; D016875:tau Proteins / Q000032:analysis
D016229:Amyloid beta-Peptides; D016708:Synaptophysin; D016875:tau Proteins