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Pathology
The post-mortem neuropathologic evaluation includes a uniform structured assessment of AD pathology, cerebral infarcts, Lewy body disease, and other pathologies common in aging and dementia. The procedures follow those recommended by the National Alzheimer's Disease Coordinating Center (NACC). Pathologic diagnoses of AD use NIA-Reagan and modified CERAD criteria, and the staging of neurofibrillary pathology uses Braak Staging.
Subcategories
Alzheimer's disease
Pathologic indices and diagnoses of Alzheimer's disease
| A score | Amyloid beta plaque score based on Thal plaque phase (4 levels) |
|---|---|
| Braak stage | Semiquantitative measure of neurofibrillary tangles |
| B score | NFT stage (4 levels), derived from Braak Stage |
| CERAD score | Semiquantitative measure of neuritic plaques |
| C score | Neuritic plaque score (4 levels), derived from CERAD |
| AD neuropathologic change (4 levels) | AD neuropathologic change based on NIA-AA criteria - 4 levels |
| AD neuropathologic change (2 levels) | AD neuropathologic change based on NIA-AA criteria - 2 levels |
| NIA-Reagan diagnosis of AD - OLD | NIA-Reagan Diagnosis of Alzheimer's disease - 4 levels (none to high likelihood) |
| NIA-Reagan diagnosis of AD (dichotomous) - OLD | Presence of AD based on NIA-Reagan diagnosis criteria - dichotomous |
| Global neuritic plaque-tangle burden | Global neuritic plaque-tangle burden (5 regions) |
| Global AD pathology burden - OLD | Global burden of AD pathology based on 5 regions |
Beta-Amyloid
Immunohistochemical Beta-amyloid
| Diffuse plaque burden | Diffuse plaque summary based on 5 regions |
|---|---|
| Neuritic plaque burden | Neuritic plaque summary based on 5 regions |
| Amyloid density (8 regions) | Amyloid density after square root transformation |
| Amyloid - OLD | Overall amyloid level - Mean of 8 brain regions |
Neurofibrillary tangles
Semiquantitative and quantitative measures of neurofibrillary tangles (NFT)
| Neurofibrillary tangles (NFT) | Semi-quantitative summary measure from 5 brain regions |
|---|---|
| Tangle density (8 regions) | Tangle density after square root transformation |
| PHF Tau Tangle Density - OLD | Quantitative summary measure from 8 brain regions |
Lewy body/PD
Nigral, limbic, and neocortical Lewy bodies as identified on sections stained with alpha-synuclein
| Lewy body disease | Pathologic diagnosis of Lewy body disease - 4 stages |
|---|---|
| Lewy bodies (7 regions) | Presence of Lewy bodies in 7 regions (includes amygdala) |
Vascular - Infarcts (Presence of)
Presence (yes vs no) of vascular infarctions
| Presence of one or more gross chronic infarcts | Cerebral Infarctions - Binary - Gross-Chronic-Any Location |
|---|---|
| Presence of one or more chronic microinfarcts | Cerebral Infarctions - Binary - Micro-Chronic-Any Location |
| Presence of one or more chronic infarcts | Cerebral Infarctions - Binary - Chronic-Any Size/Location |
Vascular - General measures
Measures of vascular disease pathology
| Cerebral atherosclerosis | Cerebral Atherosclerosis Rating - 4 levels (None - severe) |
|---|---|
| Cerebral amyloid angiopathy | Cerebral amyloid angiopathy - 4 stages |
| Arteriolosclerosis | Arteriolosclerosis - 4 stages |
Hippocampal sclerosis
Neuronal cell loss and gliosis in the hippocampus
| Presence of hippocampal sclerosis | Presence of hippocampal sclerosis in mid-hippocampus |
|---|
TDP-43
TDP-43: Hyper-phosphorylated, ubiquitinated and cleaved transactive response (TAR) DNA-binding protein 43
| TDP-43 stage | TDP-43 pathology - 4 stages (8 regions) |
|---|
Autopsy - General
General measures collected during autopsy such as time from death to autopsy procedure
| Post-mortem interval | Time interval in hours from time of death to autopsy |
|---|
Microglia
Hippocampal microglia data are available in a subset of MAP participants. Immunohistochemistry for microglia was performed using an Automated Leica Bond immunostainer (Leica Microsystems Inc., Bannockborn IL) and anti-human HLA-DP, DQ, DR antibodies (clone CR3/43; DakoCytomation, Carpinteria CA; 1:100) and (clone CR3/43; Abcam, ab7856; 1:100) using standard Bond epitope retrieval and detection. An investigator blinded to clinical and pathologic diagnoses outlined the region of interest on each slide using the Microbrightfield Stereo Investigator 8.0 software. Counting frame parameters were set up to sample 15.0% of each subregion at 400× magnification. Morphologic stages of microglia were marked in each counting frame with Stages 1 and 1d being least reactive and Stages 2 and 3 being most reactive. Counts were then upweighted by the stereology software to estimate total number of microglia by each stage in the defined area. Data for each region were collected from two adjacent blocks of tissue (0.5 to 1 cm apart).