Table 2. Minimum recommended brain regions to be sampled and evaluated.
Each brain region should receive a hematoxylin and eosin (H&E) stain. In addition, regions are recommended for additional stains to reveal AD neuropathologic change and LBD. A tiered approach to assessment of Aβ/amyloid plaques and LBD is recommended to reflect their typically ordered appearance in brain. While NFTs also typically follow an ordered appearance we recommend wider screening to assist in capturing other tauopathies. H&E-stained sections for screening in the evaluation for microvascular lesions (MVLs) and hippocampal sclerosis (HS) are designated. MLVs can occur in any region of brain and these should be reported; however, MVLs only within these screening sections are recommended for estimating possible contribution to cognitive impairment. Other lesions should be sampled as appropriate.
| AD | LBD | MVLs & HS | |||
|---|---|---|---|---|---|
| A | B | C | |||
| Region | Stain for Aβ/amyloid plaques4 | Stain for NFTs | Stain for NPs | Stain for LBs | H&E |
| Medulla including DMV | 1o: IHC or H&E3 | ||||
| Pons including LC | 1o: IHC or H&E3 | ||||
| Midbrain including SN | 3o: if 2o is + | 1o: IHC or H&E3 | |||
| Cerebellar cortex and dentate n. | 3o: if 2o is + | ||||
| Thalamus and subthalamic n.1 | MVL | ||||
| Basal ganglia at level of AC with basal nucleus of Meynert1 | 2o: if 1o is + | Consider | MVL | ||
| Hippocampus and EC1 | 2o: if 1o is +2 | Yes | Consider | 2o: IHC in at least one if 1o is + | HS |
| Cingulate, anterior | |||||
| Amygdala | 1o: IHC3 | ||||
| Middle frontal gyrus1 | 1o 2 | Yes | Yes | 2o: IHC in at least one if 1o is + | MVL |
| Superior & middle temporal gyri1 | 1o 2 | Yes | Yes | MVL | |
| Inferior parietal lobule1 | 1o 2 | Yes | Yes | MVL | |
| Occipital cortex (BA 17 & 18)1 | Consider | Yes | Consider | MVL | |
| WM at ACA, MCA, and PCA watershed | Consider | ||||
Consider taking bilateral sections if both cerebral hemispheres are available
Screen leptomeningeal and parenchymal vessels for cerebral amyloid angiopathy (CAA)
Screen for LBs with immunohistochemistry or H&E in brainstem and immunohistochemistry in amygdala. If positive, then expand immunohistochemistry for LBs in brainstem, limbic, and neocortical regions.
Stains for Aβ/amyloid plaques should be considered in other regions not needed for classification, such as in the precuneus or cingulate, as neuroimaging studies indicate that these sites are among the earliest to demonstrate retention of amyloid-binding molecules, a marker of fibrillar Aβ accumulation.
Abbreviations: DMV is dorsal motor nucleus of the vagus, LC is locus ceruleus, SN is substantia nigra, AC is anterior commissure, EC is entorhinal cortex, WM is white matter, NFTs is neurofibrillary tangles, NPs is neuritic plaques, LBs is Lewy bodies, ACA is anterior cerebral artery, MCA is middle cerebral artery, PCA is posterior cerebral artery, BA is Brodmann area.