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Constantinides et al. Neuroimmunol Neuroinflammation 2020;7:120-31 I http://dx.doi.org/10.20517/2347-8659.2019.22 Page 125

no longer differed from PD or controls. This implied that the elevated τ and decreased Aβ levels in CBS
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might have been the result of the inclusion of AD patients who presented with a CBS phenotype. The
CSF profile was implemented in another study by the same study group to investigate possible differences
[25]
between AD and non-AD pathology in a CBS cohort .
In conclusion, abnormalities in classical CSF biomarkers are common in CBD. The commonly reported
elevation in τ and τ P-181 and decrease in Aβ , does not seem to be a biochemical fingerprint of CBD but
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rather is a result of the inclusion in analyses of patients with AD pathology and a CBS phenotype. Up to
30% of CBS patients have an AD-biomarker profile, which is in accordance with pathological studies. Thus,
CSF biomarkers are particularly useful tools in the in vivo discrimination of corticobasal syndrome in CBS-
non-AD and CBS-AD.

STUDIES IN MSA
[10]
An initial study on CSF Aβ in MSA reported lower levels compared to PD, PSP and controls . A different
42
study group also found lower Aβ levels in MSA compared to controls . However, several other studies
[26]
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could not establish any meaningful difference in Aβ levels in MSA compared to other Parkinsonian
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disorders or controls [11,13,15,16,20,26,27] .
Results regarding τ in MSA are conflicting, with most studies reporting an increase of τ in MSA
T
T
compared to either controls [20,28,29] or other Parkinsonian disorders [13,20,29-31] . However, some studies have
reported no difference between MSA and other Parkinsonian disorders [16,26,27] , whereas a single study has
[26]
supported that MSA patients exhibit lower τ compared to controls .
T
Few studies have included τ P-181 data in the comparison of biomarkers in MSA and other Parkinsonian
disorders. These studies did not find any difference in τ P-181 levels in MSA compared to other study
[13]
groups [15,16,20,26] . A single study has supported lower τ P-181 levels in MSA compared to PD and controls .

Two studies have included CSF biomarker indices in the differential diagnosis of MSA from related
disorders. More specifically, a study has supported that MSA patients have significantly lower τ P-181 /τ ratios
T
[20]
compared to PD . Another study posited that higher values of τ /Aβ ratio could differentiate MSA from
T
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PD with high specificity but only moderate sensitivity .
[16]
Regarding disease subtypes, MSA-C and MSA-P patients did not differ in their CSF biochemical profile in
all relevant studies [11,20,28,30] .

Clinical-biochemical correlation studies in MSA are sparse. A study correlated disease severity in MSA
[10]
with lower CSF Aβ levels . Another study supported that both τ and τ P-181 levels increased with age
T
42
[26]
in MSA . A study implementing a battery of CSF biomarkers in a cohort of diverse neurodegenerative
disorders could not establish any correlation between CSF biomarkers and clinical characteristics . In
[15]
conclusion, data on classical CSF biomarkers are largely inconclusive.
STUDIES IN DLB
It is well documented that CSF Aβ in DLB is decreased compared to controls [14,32-36] , PD [35,37,38] and
42
parkinson’s disease dementia (PDD) [35,37,39] according to the majority of studies on the subject. Comparison
of Aβ levels between AD and DLB has yielded conflicting results, with some studies reporting greater Aβ
42
42
levels in DLB compared to AD [14,40,41] , and other studies not reporting any significant difference between the
[42]
two groups [32-34,37] . A single study reported greater Aβ values in DLB compared to controls and another
42
[40]
study did not find any difference between the two groups . Another study did not report a difference
[34]
between DLB and PDD .