Subtitle: Neurodegenerative inclusions grouped by protein: α-synuclein (Lewy bodies, GCIs), tau (tangles, Pick bodies, tufted astrocytes), TDP-43, FUS, huntingtin and Aβ, plus Hirano bodies, Bunina bodies and 10 MCQs.
Author: PathologyMCQ Editorial Board
Category: Neuropathology
Last Updated: October 2026
Read Time: 6 minutes
At-a-Glance
- Neurodegenerative diseases are classified by the aggregated protein: α-synuclein, tau, TDP-43, FUS, polyglutamine, Aβ and prion.
- α-Synucleinopathies: Lewy bodies (PD, DLB) and glial cytoplasmic inclusions (MSA).
- Tauopathies: AD tangles (3R+4R), Pick bodies (3R), PSP and CBD (4R).
- TDP-43: most ALS and about half of FTLD.
- Use IHC (synuclein, AT8 tau, TDP-43, p62) rather than H&E alone.
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Summary Table
Inclusions in neurodegenerative disease
| Inclusion | Protein | Location | Disease |
|---|---|---|---|
| Lewy body | α-synuclein | Neuronal cytoplasm | Parkinson disease, DLB |
| Glial cytoplasmic inclusion | α-synuclein | Oligodendrocyte cytoplasm | Multiple system atrophy |
| Neurofibrillary tangle | Tau (3R+4R) | Neuronal cytoplasm | Alzheimer disease, CTE |
| Senile (neuritic) plaque | Aβ (core) | Extracellular | Alzheimer disease |
| Pick body | Tau (3R) | Dentate granule cells | Pick disease |
| Tufted astrocyte | Tau (4R) | Astrocytes | Progressive supranuclear palsy |
| Astrocytic plaque | Tau (4R) | Astrocytes | Corticobasal degeneration |
| TDP-43 inclusions | TDP-43 | Neuronal and glial | ALS, FTLD-TDP |
| FUS inclusions | FUS | Neuronal | FTLD-FUS, some juvenile ALS |
| Intranuclear inclusion | Huntingtin (polyQ) | Neuronal nucleus | Huntington disease |
| Kuru and florid plaques | Prion protein | Extracellular | Kuru, variant CJD |
α-Synuclein Inclusions
- Lewy bodies: round eosinophilic cytoplasmic inclusions with a pale halo in pigmented neurons of the substantia nigra (brainstem type) or cortex (cortical type, less distinct).
- Lewy neurites accompany Lewy bodies; Braak staging for PD tracks spread from medulla to cortex.
- MSA: flame or sickle-shaped glial cytoplasmic inclusions in oligodendrocytes.
Tau Inclusions
- Alzheimer disease: neurofibrillary tangles (flame-shaped) and neuritic plaques; staged by the ABC score (Thal amyloid phase, Braak NFT stage, CERAD neuritic plaques).
- Pick disease: round, argyrophilic 3R-tau Pick bodies; ballooned Pick cells.
- PSP: globose tangles and tufted astrocytes (4R). CBD: astrocytic plaques and ballooned neurons (4R).
A step-by-step comparison: 5 ways to tell Lewy bodies from Pick bodies →
TDP-43, FUS and Polyglutamine
- TDP-43: cytoplasmic inclusions with loss of normal nuclear staining; ALS, FTLD-TDP (types A–E), and limbic-predominant age-related TDP-43 encephalopathy (LATE).
- FUS: FTLD-FUS and some young-onset ALS (FUS mutation).
- SOD1-ALS: SOD1-positive, TDP-43-negative inclusions.
- Huntington disease: intranuclear huntingtin inclusions (ubiquitin, polyQ), caudate atrophy.
Other Inclusions
Less specific inclusions
| Inclusion | Description | Seen in |
|---|---|---|
| Hirano body | Eosinophilic actin-rich rods | CA1 neurons; AD and ageing |
| Granulovacuolar degeneration | Basophilic granules in clear vacuoles | Hippocampal neurons; AD |
| Bunina body | Small eosinophilic, cystatin C positive | Lower motor neurons in ALS |
| Marinesco body | Intranuclear eosinophilic | Pigmented neurons; ageing |
| Corpora amylacea | Basophilic polyglucosan spheres | Subpial and periventricular; ageing |
Test Yourself: 10 MCQs
Neurodegenerative inclusions: 10 MCQs
Synuclein, tau, TDP-43 and more, with instant explanations.
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More practice: the CNS tumours MCQ bank →
Exam Pearls
- Synuclein: Lewy bodies (PD, DLB), GCIs (MSA).
- Tau: NFT (AD, 3R+4R), Pick body (3R), tufted astrocytes (PSP, 4R), astrocytic plaques (CBD, 4R).
- TDP-43: most ALS and FTLD-TDP; Bunina bodies in ALS.
- Huntingtin: intranuclear inclusions in the striatum.
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Related reads: Lewy body vs Pick body → · Central chromatolysis →
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References
- Love S, Perry A, Ironside J, Budka H, eds. Greenfield’s Neuropathology. 9th ed. CRC Press; 2015.
- Montine TJ, et al. National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Acta Neuropathol. 2012;123:1–11.
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