Jw. Ashford et al., NEUROPIL THREADS ARE COLLINEAR WITH MAP2 IMMUNOSTAINING IN NEURONAL DENDRITES OF ALZHEIMER BRAIN, Journal of neuropathology and experimental neurology, 57(10), 1998, pp. 972-978
Alzheimer disease (AD) neuropathology includes neuropil threads (NTs)
and neurofibrillary tangles (NFTs). In tangle-bearing neurons, the nor
mal cytoskeleton is severely disrupted and replaced with paired helica
l filament (PHF) aggregates of aberrantly phosphorylated microtubule-a
ssociated protein tau. In this study, double-label immunocytochemistry
was used to clarify the relationship between the appearance of neurof
ibrillary pathology (NTs and NFTs) and the loss of normal cytoskeletal
components, such as microtubule-associated protein 2 (MAP2) in 13 AD
cases and 6 nondemented elderly control individuals. Brain areas exami
ned included neocortex (cingulate, motor, and inferior parietal cortic
es), hippocampus, and entorhinal cortex. In mildly affected neurons, P
HF-1 immunostained NTs were found in dendrites, frequently at dendriti
c branch points, and were adjacent to MAP2 immunostaining. In more sev
erely affected neurons, the PHF-1 immunoreactivity occupied distinct d
endritic segments and appeared to displace MAP2. Interspersed MAP2 imm
unopositive dendritic segments were often beaded in appearance. In all
instances where dendrites with NTs could be traced back to the some,
the soma also contained PHF-1 immunostained fibrils in various stages
of NFT formation. The results suggest that PHFs gradually displace nor
mal microtubules in dendrites, and cause degeneration of dendritic seg
ments between NTs.