Alpha- and gamma-synuclein proteins are present in cerebrospinal fluid and are increased in aged subjects with neurodegenerative and vascular changes.
BACKGROUND
Disease-specific biomarkers should reflect a fundamental feature of neuropathology and be validated in neuropathologically confirmed cases. Several synaptic proteins have been described in cerebrospinal fluid (CSF) of patients with dementia. In Lewy body disease alpha-synuclein is incorporated within Lewy bodies and alpha-, beta- and gamma-synucleins in dystrophic neuritis. These pathological changes are expected to be seen in CSF.


METHODS
A total of 25 CSF post-mortem samples (8 control and 17 subjects with dementia) were used to quantify alpha- and gamma-synucleins and IgG.


RESULTS
We describe for the first time the presence of gamma-synuclein in CSF. There is an elevation of both alpha- and gamma-synucleins in CSF from elderly individuals with Alzheimer's disease, Lewy body disease (LBD) and vascular dementia (CVD), compared to normal controls. gamma-Synuclein showed a greater elevation in LBD, IgG in CVD. The elevation of alpha- and gamma-synucleins was seen from Braak stage III onwards and remained stable until Braak stage VI. These results were not influenced by age at death or post-mortem delay.


CONCLUSIONS
The reported increases in alpha- and gamma-synucleins and IgG in the ventricular CSF of individuals with dementia are novel findings. They now need to be explored further using a greater number of cases in each subgroup, using lumbar CSF samples to determine their applicability and relevance to a clinical diagnostic setting. It needs to be established whether using these markers may help to discriminate LBD from other types of neurodegenerative and vascular dementias.
Mukaetova-Ladinska
E B
EB
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK. Elizabeta.Mukaetova-Ladinska@ncl.ac.uk
Milne
J
J
Andras
A
A
Abdel-All
Z
Z
Cerejeira
J
J
Greally
E
E
Robson
J
J
Jaros
E
E
Perry
R
R
McKeith
I G
IG
Brayne
C
C
Xuereb
J
J
Cleghorn
A
A
Doherty
J
J
McIntosh
G
G
Milton
I
I
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015140:Dementia, Vascular / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D008297:Male; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D051845:gamma-Synuclein / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D007074:Immunoglobulin G; D051844:alpha-Synuclein; D051845:gamma-Synuclein