NEUROPIL THREADS ARE COLLINEAR WITH MAP2 IMMUNOSTAINING IN NEURONAL DENDRITES OF ALZHEIMER BRAIN

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.