Table 2.
Neuronal subtypes and their relative vulnerabilities to neurofibrillary degeneration during Alzheimer’s disease
| Brain region | Neuronal subtype | AD stage | Vulnerability to NFTs | Immunoreactivity |
|---|---|---|---|---|
| Throughout | Excitatory neurons | Throughout | Vulnerable | Glutamate receptors, especially NMDAR1; VGLUT1 |
| Entorhinal cortex layer II | Large pyramidal neurons | Early | Vulnerable | Reelin, SMI32, Rasgrp2, Sh3bgrl2 |
| Hippocampus: subiculum | Large pyramidal neurons | Early | Vulnerable | Reelin, SMI32, Cartpt |
| Hippocampus: CA1 | Large pyramidal neurons | Early | Vulnerable | Reelin, SMI32, Somatostatin receptor 4, NOV (CCN3) |
| Basal forebrain | Cholinergic neurons | Mid | Vulnerable | ChAT |
| Hippocampus: Dentate hilus | Mossy cells | Mid-late | Inconsistent | CGRP, PCP4 |
| Hippocampus: CA3 | Large pyramidal neurons | Late | Inconsistent | Reelin, SMI32, Gprin3, PKC-d |
| Hippocampus: CA2 | Large pyramidal neurons | Late | Inconsistent | Reelin, SMI32, Cacng5, PCP4, IGFBP5, NT3 |
| Hippocampus: Dentate gyrus layers III and V to VI | Granule neurons | Late | Relatively resistant | Prox1, calbindin, PCP4, IGFBP5, NT3 |
| Locus coeruleus | Noradrenergic neurons | Late | Vulnerable | NET |
| Neocortex: layer III and V | Large pyramidal neurons | Late | Vulnerable | Reelin, SMI32 |
| Primary visual cortex: layers V and VI | Pyramidal neurons | Late | Relatively resistant | Calca |
| Throughout | Inhibitory neurons | N/A | Relatively resistant | Parvalbumin, somatostatin, calbindin, calretinin; GAD; GABA receptors |
| Neocortex: layer II, upper III, VI | Small pyramidal neurons | N/A | Moderately resistant | Unknown |
| Neocortex: layer IV | Smooth stellate neurons | N/A | Relatively resistant | Unknown |
| Neocortex: layer IV | Spiny stellate neurons | N/A | Relatively resistant | Unknown |
| Cerebellum | Purkinje cells | N/A | Resistant | PCP4 |
The disease stages in which specific neuronal subtypes are affected by NFT accumulation and most distinguishing molecular markers that have been used to describe them in humans and mouse models are summarized. The level of vulnerability is colored from red (high) to green (low) and blue (resistant).