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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
| NIA-Reagan diagnosis of AD | NIA-Reagan Diagnosis of Alzheimer's disease - 4 levels (none to high likelihood) |
|---|---|
| NIA-Reagan diagnosis of AD (dichotomous) | Presence of AD based on NIA-Reagan diagnosis criteria - dichotomous |
| Braak stage | Semiquantitative measure of neurofibrillary tangles |
| CERAD score | Semiquantitative measure of neuritic plaques |
| Global AD pathology burden | Global burden of AD pathology based on 5 regions |
Beta-Amyloid
Immunohistochemical Beta-amyloid
| Amyloid | Overall amyloid level - Mean of 8 brain regions |
|---|---|
| Diffuse plaque burden | Diffuse plaque summary based on 5 regions |
| Neuritic plaque burden | Neuritic plaque summary based on 5 regions |
PHF tau tangles
Neurofibrillary tangles
| Tangles | Tangle density - Mean of 8 brain regions |
|---|---|
| Neurofibrillary tangle burden | Neurofibrillary tangle summary based on 5 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 diseases - 4 stages |
|---|
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 |
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
(in progress)
| Presence of hippocampal sclerosis (3 reg) | Presence of hippocampal sclerosis based on 3 regions |
|---|
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) |
|---|
Microglia
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) using standard Bond epitope retrieval and detection. An investigator blinded to clinical and pathologic data outlined the region of interest on each slide using a Microbrightfield Stereology System. The Stereo Investigator 8.0 software program was used to sample 4.0% of the region with a 200 x 150 μm counting frame at 400x magnification at interval grid intersection points. Stage 1 (least activated), 2, and 3 (most activated) microglia were tagged separately, and counts were upweighted by the stereology software to estimate total number of microglia in the defined area. Data for each region were collected from two adjacent blocks of tissue (0.5 to 1 cm apart).
| Total microglia density - Inferior temporal gyrus | Total density of stage 1, 2, and 3 microglia in the inferior temporal gyrus |
|---|---|
| Total microglia density - Midfrontal cortex | Total density of stage 1, 2, and 3 microglia in the midfrontal cortex |
| Total microglia density - Posterior putamen | Total density of stage 1, 2, and 3 microglia in the posterior putamen |
| Total microglia density - Ventral medial caudate | Total density of stage 1, 2, and 3 microglia in the ventral medial caudate |
| Activated microglia density (Stage 2 and 3) - Inferior temporal gyrus | Density of stage 2 and 3 activated microglia in the inferior temporal gyrus |
| Activated microglia density (Stage 2 and 3) - Midfrontal cortex | Density of stage 2 and 3 activated microglia in the midfrontal cortex |
| Activated microglia density (Stage 2 and 3) - Posterior putamen | Density of stage 2 and 3 activated microglia in the posterior putamen |
| Activated microglia density (Stage 2 and 3) - Ventral medial caudate | Density of stage 2 and 3 activated microglia in the ventral medial caudate |
| Activated microglia density (Stage 3) - Inferior temporal gyrus | Density of stage 3 activated microglia in the inferior temporal gyrus |
| Activated microglia density (Stage 3) - Midfrontal cortex | Density of stage 3 activated microglia in the midfrontal cortex |
| Activated microglia density (Stage 3) - Posterior putamen | Density of stage 3 activated microglia in the posterior putamen |
| Activated microglia density (Stage 3) - Ventral medial caudate | Density of stage 3 activated microglia in the ventral medial caudate |
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 |
|---|