Tauopathies are a group of neurodegenerative disorders characterized by the accumulation of abnormal [tau protein](/proteins/tau) aggregates in the brain. This comparison matrix covers four major tauopathies: Alzheimer's Disease (AD), Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), and Frontotemporal Lobar Degeneration with tau pathology (FTLD-tau).
| Feature | Alzheimer's Disease | Progressive Supranuclear Palsy | Corticobasal Degeneration | FTLD-tau (including CBD) |
|---------|---------------------|--------------------------------|---------------------------|--------------------------|
| Primary Protein | Tau (3R+4R) | Tau (4R) | Tau (4R) | Tau (3R or 4R depending on subtype) |
| Main Pathology | Neurofibrillary tangles, amyloid plaques | NFTs, tufted [astrocytes](/entities/astrocytes) | Astrocytic plaques, NFTs | Pick bodies (3R), CBD pathology |
| Main Genes | [APP](/genes/app), [PSEN1](/genes/psen1), [PSEN2](/genes/psen2), [APOE](/genes/apoe) | [MAPT](/genes/mapt) | [MAPT](/genes/mapt), [CBD](/genes/cbd) | [MAPT](/genes/mapt), [GRN](/genes/grn) |
Tauopathies are a group of neurodegenerative disorders characterized by the accumulation of abnormal [tau protein](/proteins/tau) aggregates in the brain. This comparison matrix covers four major tauopathies: Alzheimer's Disease (AD), Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), and Frontotemporal Lobar Degeneration with tau pathology (FTLD-tau).
| Feature | Alzheimer's Disease | Progressive Supranuclear Palsy | Corticobasal Degeneration | FTLD-tau (including CBD) |
|---------|---------------------|--------------------------------|---------------------------|--------------------------|
| Primary Protein | Tau (3R+4R) | Tau (4R) | Tau (4R) | Tau (3R or 4R depending on subtype) |
| Main Pathology | Neurofibrillary tangles, amyloid plaques | NFTs, tufted [astrocytes](/entities/astrocytes) | Astrocytic plaques, NFTs | Pick bodies (3R), CBD pathology |
| Main Genes | [APP](/genes/app), [PSEN1](/genes/psen1), [PSEN2](/genes/psen2), [APOE](/genes/apoe) | [MAPT](/genes/mapt) | [MAPT](/genes/mapt), [CBD](/genes/cbd) | [MAPT](/genes/mapt), [GRN](/genes/grn) |
| Feature | Alzheimer's Disease | Progressive Supranuclear Palsy | Corticobasal Degeneration | FTLD-tau |
|---------|---------------------|--------------------------------|---------------------------|----------|
| Core Symptoms | Memory loss, cognitive decline | Vertical gaze palsy, falls, axial rigidity | Apraxia, alien limb, cortical sensory loss | Behavior/personality changes or language loss |
| Onset Age (typical) | 65-80 years | 60-70 years | 60-70 years | 45-65 years |
| Disease Duration | 8-12 years | 5-10 years | 5-8 years | 6-12 years |
| Motor Symptoms | Late, mild | Early, prominent (gaze palsy, falls) | Early, asymmetric (apraxia, dystonia) | Late, variable |
| Cognitive Profile | Amnestic, global deficits | Frontal/executive deficits | Language + executive deficits | Behavior or language (primary) |
| Speech | Normal initially | Dysarthria common | Nonfluent aphasia possible | Nonfluent or semantic |
| Autonomic | Usually mild | Moderate | Variable | Usually mild |
| Hallucinations | Late stage | Rare | Rare | Rare |
| Feature | Alzheimer's Disease | Progressive Supranuclear Palsy | Corticobasal Degeneration | FTLD-tau |
|---------|---------------------|--------------------------------|---------------------------|----------|
| Sporadic Cases | ~95% | ~95% | ~60% | ~60% |
| Familial Cases | ~5% | ~5% | ~40% | ~40% |
| Major Risk Genes | [APP](/genes/app), [PSEN1](/genes/psen1), [PSEN2](/genes/psen2), [APOE4](/genes/apoe4), [TREM2](/genes/trem2) | [MAPT](/genes/mapt), [STX6](/genes/stx6) | [MAPT](/genes/mapt) | [MAPT](/genes/mapt), [GRN](/genes/grn) |
| Inheritance | Autosomal dominant (rare), complex | Usually sporadic | Usually sporadic | Autosomal dominant common |
| Tau Isoforms | 3R + 4R | 4R | 4R | 3R (Pick's) or 4R (CBD/PSP) |
| Feature | Alzheimer's Disease | Progressive Supranuclear Palsy | Corticobasal Degeneration | FTLD-tau |
|---------|---------------------|--------------------------------|---------------------------|----------|
| Key Inclusions | Neurofibrillary tangles | NFTs, tufted astrocytes | Astrocytic plaques, CBD lesions | Pick bodies (Pick's), ballooned [neurons](/entities/neurons) |
| Tau Morphology | Paired helical filaments | Straight filaments | Straight filaments | 3R tau (Pick's), 4R tau (CBD) |
| Primary Regions | [Hippocampus](/brain-regions/hippocampus), [entorhinal cortex](/brain-regions/entorhinal-cortex) | Brainstem, basal ganglia | Motor [cortex](/brain-regions/cortex), basal ganglia | Frontal/temporal cortex |
| Amyloid | Present (Aβ plaques) | Absent | Absent | Absent (except AD overlap) |
| Cell Loss | Hippocampus, cortex | Substantia nigra, globus pallidus | Motor/premotor cortex | Frontotemporal cortex |
| Region | Alzheimer's Disease | Progressive Supranuclear Palsy | Corticobasal Degeneration | FTLD-tau |
|--------|---------------------|--------------------------------|---------------------------|----------|
| Frontal Cortex | Late involvement | Early | Early | Early, prominent |
| Temporal Cortex | Early | Late | Variable | Early, prominent |
| Parietal Cortex | Early | Late | Variable | Variable |
| Occipital Cortex | Late | Late | Late | Usually spared |
| Hippocampus | Very early | Late | Rare | Variable |
| Basal Ganglia | Moderate | Early, severe | Early, severe | Variable |
| Brainstem | Late | Early, severe | Midbrain | Usually spared |
| Cerebellum | Usually spared | Variable | Variable | Usually spared |
| Feature | Alzheimer's Disease | Progressive Supranuclear Palsy | Corticobasal Degeneration | FTLD-tau |
|---------|---------------------|--------------------------------|---------------------------|----------|
| Symptomatic | [Cholinesterase inhibitors](/entities/cholinesterase-inhibitors), memantine | Limited | Limited | Limited |
| Cognitive | Cholinesterase inhibitors | None proven | None proven | None proven |
| Motor | Limited | Physical therapy | Botulinum toxin, therapy | Variable |
| Disease-Modifying | Aducanumab, [lecanemab](/entities/lecanemab) (anti-amyloid) | None approved | None approved | None approved |
| Clinical Trials | Anti-tau therapies in progress | Anti-tau therapies | Anti-tau therapies | Anti-tau therapies |
| Feature | Alzheimer's Disease | Progressive Supranuclear Palsy | Corticobasal Degeneration | FTLD-tau |
|---------|---------------------|--------------------------------|---------------------------|----------|
| MRI | Hippocampal atrophy | Midbrain ("hummingbird"), PSP signs | Asymmetric cortical atrophy | Frontotemporal atrophy |
| PET | amyloid-PET positive | Tau-PET may show midbrain | Tau-PET variable | Tau-PET may show frontal |
| CSF Biomarkers | [Aβ42](/proteins/amyloid-beta) low, t-tau high, p-tau high | Tau elevated, Aβ normal | Tau elevated | Tau normal to elevated |
| DaT Scan | Usually normal | Reduced uptake | Reduced uptake | Usually normal |
| Feature | Alzheimer's Disease | Progressive Supranuclear Palsy | Corticobasal Degeneration | FTLD-tau |
|---------|---------------------|--------------------------------|---------------------------|----------|
| Hallmark Sign | Memory impairment | Vertical supranuclear gaze palsy | Alien limb phenomenon | Behavior change or language loss |
| Tau Isoform | 3R + 4R | 4R | 4R | 3R or 4R |
| Amyloid | Present | Absent | Absent | Absent |
| Age at Onset | Older | 60-70 | 60-70 | Younger (45-65) |
| Disease Progression | Gradual | Rapid | Variable | Variable |