
Dementia is a syndrome, a common pattern of signs and symptoms that is caused by more than one disease. Specific diseases that cause dementia, such as Alzheimer’s disease (AD), are clinico-pathologic entities meaning that their diagnosis requires both certain clinical (functional) features and certain pathologic (structural) features. Some structural features can be determined by neuroimaging studies like MRI; however, the definitive structural changes of dementing diseases require microscopic examination.
Classically, microscopic examination of specific brain regions uses dyes or other chemicals that react with molecules in brain, an area of research called histochemistry. Indeed, Dr. Alzheimer used a silver salt to react with tissue to reveal the now famous senile plaques and neurofibrillary tangles that are characteristic of the disease that bears his name.
A more recent advance is immunohistochemistry, a method that uses antibodies to investigate specific proteins or protein modifications in specific brain regions. Biochemical and genetic research have highlighted a group of proteins that appear to be central to the specific diseases that cause dementia. Immunohistochemistry is used to probe for these proteins and to highlight the pathologic structures where they are located in brain.
| Protein(s) detected by IHC |
Pathologic Structure |
Dementing Disease(s) |
Amyloid (A) β-Peptides |
Senile Plaques |
Alzheimer’s Disease |
| Microtubule Associated Protein (MAP) Tau |
Neurofibrillary tangles |
Alzheimer’s Disease |
| Pick Bodies |
Pick’s Disease |
| Other Neuronal or Glial Inclusions |
Corticobasal degeneration, Some Fronto-Temporal Lobar Degenerations |
| α-Synuclein |
Lewy Body |
Parkinson’s Disease,
Dementia with Lewy Bodies |
| Glial Cytoplasmic Inclusion |
Multuple System Atrophy |
| TAR DNA binding protein (TDP-43) |
Neuronal inclusions |
Some Fronto-Temporal Lobar Degenerations, Other diseases |
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