Table 2.
Clinical evidence supporting the role of Tau in PD pathophysiology
| Type of sample | Cohorts | Findings | Citation (Year) |
|---|---|---|---|
| CSF |
N = 70 -PDND (n = 20) -PDD (n = 20) -HC (n = 30) |
CSF t-Tau and p-Tau levels: -higher in PDD than PDND and HC -associate with impaired memory and naming in PD |
Compta et al. (2009) |
| CSF |
N = 62 -PD (n = 32) -HC (n = 30) |
1. Higher Tau and clusterin levels in PD versus HC 2. Higher Tau, Tau/Aβ42 and clusterin in patients suffering from PD less than 2 years versus those more than 2 years |
Přikrylová Vranová et al. (2010) |
| CSF |
N = 165 -PD (n = 109) -AD (n = 20) -HC (n = 36) |
CSF t-Tau and p-Tau levels: -no different in HC versus PD without treatment |
Alves et al. (2010) |
| CSF |
N = 345 -PD (n = 49) -PD-CIND (n = 62) -PDD (n = 11) -AD (n = 49) -aMCI (n = 24) -HC (n = 150) |
CSF t-Tau and p-Tau levels: -unchanged in PD-CIND and PDD CSF Aβ42 levels: -reduced in PD-CIND and PDD |
Montine et al. (2010) |
| CSF |
N = 121 -PDD (n = 21) -AD (n = 45) -DLB (n = 15) -HC (n = 40) |
CSF Tau levels: -no difference between PDD and HC CSF Aβ levels: -lower in PDD versus HC |
Bibl et al. (2010) |
| CSF |
N = 56 -TDPD (n = 6) -NTPD (n = 6) -AD (n = 27) -HC (n = 17) |
CSF t-Tau and Tau/Aβ42 levels: -significantly increased in both NTPD and AD compared with TDPD and HC groups |
Jellinger (2012) |
| CSF |
N = 22 -PD |
CSF Aβ42, Aβ42/t-Tau, BDNF levels: -have significant associations with cognitive impairment in non-demented PD patients |
Leverenz et al. (2011) |
| CSF |
N = 181 -PD (n = 38) -DLB (n = 32) -AD (n = 48) -FTD (n = 31) -HC (n = 32) |
1. Aβ42, t-Tau and p-Tau levels in PD patients were similar to controls 2. T-Tau/α-Syn and p-Tau/α-Syn showed the lowest values in PD patients |
Parnetti et al. (2011) |
| CSF |
PD (n = 48) -EDO-PD (n = 17) -TD-PD (n = 15) -NT-PD (n = 16) AD (n = 18) HC (n = 19) |
In PD patients: -Tau and Tau/Aβ42 levels higher in NT-PD versus the other groups -Tau levels have a close relationship with motor manifestation in NT-PD |
Přikrylová Vranová et al. (2012) |
| CSF |
N = 403 -PD |
Cross-sectional analyses: -baseline CSF biomarker levels positively correlated with each other -baseline CSF p-Tau/t-Tau and Aβ42 have borderline effects on the time to reach the endpoint Longitudinal analyses: -t-Tau and t-Tau/Aβ42 change rate are correlated with UPDRS total, or motor scores change rate |
The Parkinson Study Group DATATOP Investigators et al. (2013) |
| CSF |
N = 69 -PD (n = 44) -HC (n = 25) |
1. o/t-α-Syn and Aβ42/t-Tau ratio significantly contributing to the discrimination of PD from HC 2. Patients with low CSF Aβ42 level are more prone to develop cognitive decline |
Parnetti et al. (2014) |
| CSF |
N = 403 -PD |
CSF p-Tau and p-Tau/Aβ42 levels: -predict cognitive decline in PD since start treatment |
Liu et al. (2015) |
| CSF |
N = 390 -PD |
Combination of age, non-motor assessments, DAT imaging, and CSF Aβ42/t-Tau ratio can predict the occurrence of cognitive impairment in PD patients during 2-years follow-up study | Schrag et al. (2017) |
| CSF |
N = 285 -PD (n = 173) -HC (n = 112) |
12 years longitudinal study in PD: -Aβ42 increase in both groups -t-Tau and α-Syn levels remained stable -p-Tau increased marginally more in PD over time -p-Tau/t-Tau increased, and t-Tau/Aβ42 decreased slightly Across time points: -t-Tau, p-Tau, and α-Syn levels were significantly lower in PD versus HC |
Mollenhauer et al. (2017) |
|
CSF Neuroimaging |
PD = 421 -mild motor predominant (n = 223) -intermediate (n = 146) -diffuse malignant (n = 52) |
1. Diffuse malignant PD have lowest Aβ and Aβ/t-Tau levels in CSF 2. MRI morphometry showed more atrophy and disease-specific network in diffuse malignant PD |
Fereshtehnejad et al. (2017) |
|
CSF Plasma |
N = 115 -PD (n = 51) -HC-CSF (n = 40) -HC-Plasma (n = 24) |
1. CSF levels of α-Syn, Aβ42, and TNF-α were lower in patients than in controls 2. The t-Tau/α-Syn, p-Tau/α-Syn, t-Tau/Aβ42 + α-Syn, and p-Tau/Aβ42 + α-Syn ratios were higher in patients 3. P-Tau/α-Syn alone and also combined with TNF-α obtained the best AUC 4. IL-6 positively correlated with UPDRS scores |
Delgado-Alvarado (2017) |
| CSF |
cohort 1 -PD (n = 281) cohort 2 -PD (n = 40) |
1. T-Tau/Aβ42, t-Tau/α-Syn, t-Tau/Aβ42 + α-Syn, Aβ42/t-Tau ratios are associated with dementia risk over a 3-year follow-up 2. T-Tau/α-Syn and t-Tau/Aβ42 + α-Syn ratios are associated with progression to dementia over a 41-month follow-up |
Delgado-Alvarado et al. (2018) |
| CSF |
N = 136 -DLB (n = 51) -PD (n = 53) -HC (n = 32) |
CSF Tau and p-Tau levels: -higher Tau levels in DLB versus PDD -higher Tau levels in PDD versus PD -Tau levels no difference between PD and HC -both reflect severity of dementia in PDD and DLB CSF p-Tau/Tau levels: -lower in DLB versus PDD |
Gmitterová (2018) |
| CSF |
N = 68 -PD (n = 30) -CBS (n = 11) -CBD (n = 8) -HC (n = 19) |
1. 24-OHC levels increased in PD or CBS patients 2. CSF 24-OHC, Tau and p-Tau levels in PD, CBS or CBD patients correlate with each other |
Björkhem et al. (2018) |
| CSF |
N = 230 -PDND (n = 120) -HC (n = 110) |
1. P-Tau levels were significantly lower in the PD group and rose significantly during the 1-year follow-up time in the PD group 2. T-Tau levels were different between the two groups at all time points despite their non-significant longitudinal changes |
Dolatshahi et al. (2018) |
| CSF |
N = 557 -PD (n = 415) -HC (n = 142) |
10-year follow-up study of sporadic PD -low levels of Aβ42 are associated with a higher risk of developing cognitive impairment earlier in the disease process |
Lerche et al. (2019) |
| Neuroimaging |
PD (n = 30) -PD-CN (n = 15) -PD-MCI (n = 15) HC (n = 49) |
Patterns of cortical Tau and Aβ do not differ in three groups | Winer et al. (2018) |
| Neuroimaging |
N = 17 -PD |
No significant increase in Tau tangles occurred after a two-year follow-up of PD patients | Hansen et al. (2020) |