Categories


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

Hippocampal sclerosis (Typical) Definite presence of typical hippocampal sclerosis

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

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