Frontotemporal lobar degeneration
- Lesion
Frontotemporal degeneration shrinks the frontal and temporal lobes, changing personality and language; tau or TDP-43 clumps cause it.
What it is
Frontotemporal lobar degenerations are a group of diseases that destroy the frontal and temporal lobes and cause behavioural variant frontotemporal dementia or progressive aphasias, often before age 65. They are classified by the aggregated protein: tau (FTLD-tau) or TDP-43 (FTLD-TDP), with rarer FUS forms. Progressive supranuclear palsy and corticobasal degeneration are tauopathies that cause atypical parkinsonism. Many cases are inherited, and FTLD-TDP overlaps with ALS.
Step by step
- A tau or TDP-43 problem starts, from a mutation or spontaneously.
- TDP-43 leaves the nucleus and aggregates in the cytoplasm, or tau detaches from microtubules.
- Neurons in frontal and anterior temporal circuits lose function.
- Atrophy advances; behaviour, social cognition and language decline.
- Spread to motor neurons (ALS) or brainstem nuclei (PSP) adds motor features.
Frontotemporal lobar degenerations and atypical parkinsonism
| Disease | Protein | Signature lesion | Clinical picture |
|---|---|---|---|
| Pick disease | Tau (3-repeat) | Pick bodies, ballooned neurons | Behavioural change, aphasia |
| Progressive supranuclear palsy | Tau (4-repeat) | Globose tangles, tufted astrocytes | Vertical gaze palsy, falls, axial rigidity |
| Corticobasal degeneration | Tau (4-repeat) | Astrocytic plaques, ballooned neurons | Asymmetric rigidity, apraxia, alien limb |
| FTLD with MAPT mutation | Tau | Neuronal and glial tau | Familial FTD with parkinsonism |
| FTLD-TDP (C9orf72, GRN) | TDP-43 | Ubiquitinated TDP-43 inclusions | Behavioural FTD, aphasia, with or without ALS |
Clinical notes
- Early disinhibition, apathy, loss of empathy and compulsive behaviour, with memory relatively spared at first.
- Family history is common: genetic counselling matters.
Test yourself
Think of the answer, then tap the question to see it.
What are Pick bodies?
Round, silver-staining tau inclusions in neurons, characteristic of Pick disease.
Which gene expansion links frontotemporal dementia and ALS?
The C9orf72 hexanucleotide repeat expansion.
Which eye movement problem is characteristic of progressive supranuclear palsy?
Vertical gaze palsy, especially looking down.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Frontotemporal dementia with parkinsonism-17: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.