Tauopathies are a group of neurodegenerative disorders characterized by the accumulation of abnormal tau protein 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 |
Astrocytic plaques, NFTs |
Pick bodies (3R), CBD pathology |
| Main Genes |
APP, PSEN1, PSEN2, APOE |
MAPT |
MAPT, CBD |
MAPT, 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, PSEN1, PSEN2, APOE4, TREM2 |
MAPT, STX6 |
MAPT |
MAPT, 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 |
| Tau Morphology |
Paired helical filaments |
Straight filaments |
Straight filaments |
3R tau (Pick's), 4R tau (CBD) |
| Primary Regions |
Hippocampus, entorhinal cortex |
Brainstem, basal ganglia |
Motor 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, 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 (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 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 |
flowchart TB
subgraph Tauopathies
A["Tauopathies"] --> B["3R+4R Tauopathies"]
A --> C["4R Tauopathies"]
A --> D["3R Tauopathies"]
B --> B1["Alzheimer's Disease"]
B1 --> B2["Paired Helical Filaments"]
C --> C1["Progressive Supranuclear Palsy"]
C --> C2["Corticobasal Degeneration"]
C1 --> C3["Straight Filaments - 4R"]
C2 --> C4["Astrocytic Plaques - 4R"]
D --> D1["Pick's Disease"]
D1 --> D2["Pick Bodies - 3R"]
end
style B1 fill:#e3f2fd
style C1 fill:#fff3e0
style C2 fill:#fff3e0
style D1 fill:#e8f5e9
flowchart LR
subgraph AD_Pathogenesis
A1["Amyloid-beta plaques"] --> B1["Tau hyperphosphorylation"]
B1 --> C1["Neurofibrillary tangles"]
C1 --> D1["Synaptic loss & neuronal death"]
end
subgraph PSP_Pathogenesis
A2["MAPT mutations"] --> B2["4R tau overexpression"]
B2 --> C2["Tau filament formation"]
C2 --> D2["Glial pathology - tufted astrocytes"]
D2 --> E2["Neuronal loss in brainstem"]
end
subgraph CBD_Pathogenesis
A3["MAPT mutations"] --> B3["4R tau accumulation"]
B3 --> C3["Neuronal inclusions"]
C3 --> D3["Astrocytic plaques"]
D3 --> E3["Cortical degeneration"]
end
subgraph FTLD_Pathogenesis
A4["GRN mutations"] --> B4["Progranulin deficiency"]
B4 --> C4["Tau dysfunction"]
C4 --> D4["Pick bodies / NFT"]
D4 --> E4["Frontotemporal degeneration"]
end