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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 123

b
a
Mollenhauer et al. [32] ↓ ↔ b ↓ ↔ a ↑ a a. ctrl
b. AD
b
Mollenhauer et al. [33] ↓ ↔ b ↓ ↑ a ↔ b a. ctrl
a
b. AD
a
Mulugeta et al. [34] ↓ ↔ b ↔ c ↔ c a. ctrl
b.AD, PDD
c. ctrl, PDD
Llorens et al. [35] ↓ a ↑ b a. ctrl, PD, PDD
b. PD, MSA
Van Steenoven et al. [36] ↓ ctrl
b
a
Parnetti et al. [37] ↓ ↔ b ↓ ↑ c ↓ b a. PD, PDD
b. AD
c. PD
Kaerst et al. [38] ↓ ↑ PD
Gmitterova et al. [39] ↓ ↑ PDD
a
a
Gómez-Tortosa et al. [40] ↑ ↔ b ↓ ↔ b a. AD
b. ctrl
Boström et al. [41] ↑ a ↓ a ↑ b a. AD
b. ctrl
Abdelnour et al. [42] ↑ ctrl
Mollenhauer et al. [43] ↔ PDD
↑: elevated CSF levels; ↓: decreased CSF levels; ↔: no difference in CSF levels; CSF: cerebrospinal fluid; AD: Alzheimer’s disease; PD:
Parkinson’s disease; MSA: multiple system atrophy; PSP: progressive supranuclear palsy; CBD: corticobasal degeneration; DLB: dementia
with Lewy bodies; PDD: parkinson's disease dementia
controls [18,19] , whereas a single study posited that patients with PSP have lower τ levels compared to CBD,
T
[12]
but higher τ levels compared to PD .
T
CSF τ P-181 does not seem to be useful in the differentiation of PSP from other causes of Parkinsonism or
controls [12,14-18] . Two studies have reported lower τ P-181 levels compared to controls [13,19] .

Few studies include data on ratios of CSF biomarkers. In a large study, which included PSP, CBD and
AD patients, elevated τ P-181 /Aβ ratio values could differentiate AD from PSP and CBD . Another study
[17]
42
posited that lower τ P-181 / τ ratio values could discriminate patients with atypical Parkinsonism (PSP and
T
MSA) from PD . This ratio was optimal for discriminating PSP from CBD with a reported sensitivity of
[20]
[12]
86% and specificity of 75% . PSP patients could also be differentiated from controls by lower Aβ /τ T [12]
42
and higher τ /τ P-181 [16] ratios.
T
A single study examined classical CSF biomarkers in different phenotypes of PSP. To this end, patients
with classic Richardson’s syndrome (RS) were compared to patients with PSP-Parkinsonism (PSP-P).
Interestingly, only patients with PSP-P had elevated total τ levels, compared to RS, PD and controls. Aβ
42
T
[20]
on the other hand was significantly lower in RS patients compared to PSP-P .
Few PSP patients seem to harbor a CSF-AD profile (generally defined as decreased Aβ with elevated τ
T
42
or τ P-181 ). In a large cohort, including diverse neurodegenerative disorders, 10% of PSP patients had a CSF-
AD profile, as determined by an index incorporating CSF Aβ and τ P-181 values . Likewise, only one of 19
[14]
42
PSP patients (~5%) had a typical CSF-AD profile, as determined by abnormal Aβ , τ and τ P-181 values, in a
T
42
[16]
cohort of patients with Parkinsonism .
Lastly, the possible relationship between CSF biomarkers and clinical characteristics has also been
extensively studied in PSP. Most studies agree that there is no clinical-biochemical correlation in PSP [12-15,17] .
Two studies have correlated low Aβ levels with higher disease severity, as measured by Hoehn and Yahr
42
score or the PSP Rating Scale .
[10]
[19]