[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Central nervous system](https://durgical.com/en/general-pathology/areas/cns/) › Frontotemporal lobar degeneration

# Frontotemporal lobar degeneration

- Lesion

Frontotemporal degeneration shrinks the frontal and temporal lobes, changing personality and language; tau or TDP-43 clumps cause it.

Updated Nov 12, 2026

## Key points

- Gross: knife-edge atrophy of frontal and temporal lobes, sparing the back of the superior temporal gyrus.
- Pick disease: round argyrophilic tau inclusions (Pick bodies) and swollen neurons (Pick cells).
- Progressive supranuclear palsy: vertical gaze palsy, early falls, axial rigidity; globose tangles and tufted astrocytes in brainstem and basal ganglia.
- Corticobasal degeneration: asymmetric rigidity, apraxia, alien limb; astrocytic plaques and ballooned neurons.
- FTLD-TDP genes: C9orf72 hexanucleotide repeat expansion (also the commonest familial ALS), GRN (progranulin) and others; MAPT mutations cause familial FTLD-tau.

## 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](https://durgical.com/en/conditions/frontotemporal-dementia/) | Tau (3-repeat) | Pick bodies, ballooned neurons | Behavioural change, aphasia |
| [Progressive supranuclear palsy](https://durgical.com/en/conditions/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)](https://durgical.com/en/conditions/amyotrophic-lateral-sclerosis/) | 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.

## Memory aid

Front and side go first: manners and words fade; tau or TDP is to blame.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/frontotemporal-lobar-degeneration/)

[More Pathology questions →](https://durgical.com/en/practice/?f=pathology)

## Elsewhere in DurgiPedia

- [Basal ganglia and movement control](https://durgical.com/en/physiology/basal-ganglia-and-movement-control/)

## Connections

## Related 5

- [Neurodegeneration: the protein table](https://durgical.com/en/general-pathology/neurodegeneration-the-protein-table/)
- [Alzheimer disease: plaques and tangles](https://durgical.com/en/general-pathology/alzheimer-disease-plaques-and-tangles/)
- [Motor neuron diseases](https://durgical.com/en/general-pathology/motor-neuron-diseases/)
- [Parkinson disease and Lewy body disorders](https://durgical.com/en/general-pathology/parkinson-disease-and-lewy-body-disorders/)
- [Nonclassic inheritance: repeat expansions, mitochondrial genes, imprinting, mosaicism](https://durgical.com/en/general-pathology/nonclassic-inheritance-repeat-expansions-mitochondrial-genes-imprinting-mosaicis/)

## Related conditions 4

- [Frontotemporal dementia](https://durgical.com/en/conditions/frontotemporal-dementia/)
- [Progressive supranuclear palsy](https://durgical.com/en/conditions/progressive-supranuclear-palsy/)
- [Amyotrophic lateral sclerosis](https://durgical.com/en/conditions/amyotrophic-lateral-sclerosis/)
- [Dementia (major neurocognitive disorder)](https://durgical.com/en/conditions/dementia/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://medlineplus.gov/genetics/condition/frontotemporal-dementia-with-parkinsonism-17/) (MedlinePlus, US National Library of Medicine, 2026).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/general-pathology/frontotemporal-lobar-degeneration/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/frontotemporal-lobar-degeneration/