Table 3.

Illustrating the likely usefulness and limitations of cerebral biopsies in the diagnosis of neurodegenerative diseases

Disease	Likely usefulness of cerebral biopsy	Frontal or temporal site preferred (F/T)	Stains recommend in first instance	Secondary stains confirmatory	Secondary stains to exclude other diagnoses	Other information required	Comments
AD (IV-VI)	High	F or T	HE, tau, p62, Aβ		TDP-43, α-syn	History, scans
PSP	Low	N/A	HE, p62, tau	4-R tau,	Aβ, TDP-43, α-syn	History, scans, genetics	Negative biopsy does not exclude. Rule out MAPT mutation FTD and/or other parkinsonian diseases
				3-R tau
CBD	High	F or T	HE, p62, tau	4-R tau,	Aβ, TDP-43, α-syn	History, scans, genetics	Rule out MAPT mutation
				3-R tau
MAPT mutation	Likely to depend on mutation	N/A	HE, p62, tau	4-R tau,	Aβ, TDP-43, α-syn	History, scans, genetics	Genetics essential for diagnosis
				3-R tau
DLB	High- neocortical, Moderate-Low - limbic	F >T	HE, p62, α-syn,		Aβ, tau, TDP-43	History, scans	Often seen with AD pathology
MSA	High	F or T	HE, p62, α-syn,		tau	History, scans	White matter essential in the biopsy
HD	High	F or T	HE, p62	polyglutamine	TDP-43, FUS	History, scans, genetics	Genetics essential for diagnosis
FTLD-TDP/ FTLD-MND	High	T > F	HE, p62, TDP-43		Aβ, tau, FUS	History, scans, genetics	History to tell FTLD-MND from FTLD-TDP
ALS	Very low-nil	N/A	HE, p62, TDP-43, FUS			History, scans genetics	Biopsy-Very unlikely to help
Metabolic disease	Likely to depend on disease	N/A	HE, PAS, LFB/N		p62, tau	History, scans genetics
CVD	Depends what type: infarct-high AA-high Binswanger’s-low	N/A	HE, Aβ, CR		p62, tau, LFB/N	History, scans	Leptomeninges needed for AA, Binswanger’s likely to be missed without deep white matter
Prion Disease	Moderate-High	unknown	HE, GFAP, PrP		Aβ, tau, TDP-43, α-syn	History, scans genetics	Negative biopsy does not rule out diagnosis
FTLD-FUS	unknown	unknown	HE, p62, FUS		Aβ, tau, TDP-43, α-syn	History, scans genetics
PiD	High	unknown	HE, p62, tau	4-R tau, 3-R tau	TDP-43, Aβ, α-syn	History, scans genetics	Rule out MAPT mutation
PD	Very low-nil	N/A	HE, p62 α-syn		tau	History, scans genetics	Biopsy could rule out other causes of parkinsonism

Those cases in italics were not included in this study but features have been included and estimated from the following references [3,5,7,9]. AA amyloid angiopathy, CVD cerebrovascular disease, CR congo red, F frontal lobe, FTD frontotemporal dementia, GFAP glial fibrillary acidic protein, LFB/N Luxol fast blue/Nissl, N/A details not applicable, PAS Periodic acid Schiff, PiD Pick’s disease, PD Parkinson’s disease, PrP prion protein, α-syn α-synuclein, T temporal lobe.

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