Aims

Lewy body disease (LBD) is characterized by intracytoplasmic inclusions of alpha-synuclein (α-Syn), but α-Syn pathology is also found in patients who do not meet LBD clinical criteria, such as those with mild cognitive impairment (MCI) or Alzheimer’s dementia (AD). Protein-specific biomarkers are needed for diagnosis of underlying α-Syn pathology. Seed Amplification Assay (SAA) in the CSF holds promise to detect misfolded α-Syn in living patients, but most studies are limited to those with a clinical LBD diagnosis. Here, we investigated whether α-Syn-SAA is positive in the CSF of patients with MCI and dementia, due to either AD or LBD.

Methods

We studied 150 CSF samples from Stanford research participants adjudicated as MCI due to LBD or AD (22 MCI-LB, 25 MCI-AD), or dementia due to LBD or AD (11 dementia-LBD, 22 AD), as well as 33 healthy controls and 34 Parkinson’s disease with normal cognition (PD-nlCog). Samples were tested by the SYNTap® Biomarker Test in Amprion’s CLIA Laboratory.

Results

In cognitively normal participants (HC and PD-nlCog), SYNTap® showed 88.1% accuracy, 88.2% sensitivity and 87.9% specificity (p<0.0001). In cognitively impaired participants, SYNTap® identified 17.2% of MCI-AD and 13.6% of AD as α-Syn-SAA positive, whereas 85.7% of MCI-LB and 85.7% dementia-LB. One case diagnosed as only AD during life, who was α-Syn-SAA positive was confirmed postmortem to have AD and LBD co-pathology.

Conclusions

16% of cognitively impaired patients, who do not have a clinical diagnosis of LBD, were SAA positive.

Aims

Plasma phosphorylated tau181 (ptau181) levels are been associated with amyloid-β deposition in Alzheimer’s disease (AD). Lewy body disease (LBD) frequently presents with amyloid-β co-pathology, which influences disease progression, cognitive decline, and brain atrophy.

We aimed to evaluate whether plasma ptau181 helps to identify amyloid-β co-pathology in the LBD spectrum, and whether plasma ptau181 levels in LBD are associated with AD cerebrospinal fluid (CSF) biomarkers.

Methods

We selected 203 Stanford research participants: 97 healthy controls, 37 Parkinson’s disease with normal cognition, 39 on the LBD-spectrum (25 MCI-LB and 14 dementia-LB), and 30 on the AD-spectrum (10 MCI-AD and 20 dementia-AD). Plasma ptau181 concentrations were measured using the Lumipulse G fully automated platform from Fujirebio Diagnostics. Diagnostic accuracy was evaluated with area-under-the-curve (AUC) values from receiver-operating characteristic (ROC) analyses.

Results

Plasma ptau181 levels predicted amyloid-β positivity in LBD patients (AUC=0.726). Combining plasma ptau181 levels with age, sex, years of education, APOE e4 genotype, and global cognition (MoCA), improved the prediction of amyloid-β positivity (AUC= 0.881). Similarly, plasma ptau181 levels predicted amyloid-β positivity in MCI-LB patients (AUC=0.691). This model was improved by including age, sex, years of education, APOE E4 genotype, and MoCA (AUC=0.826).

Plasma ptau181 levels were negatively associated with CSF Aβ42/Aβ40 ratio and positively associated with CSF ptau181/Aβ40 ratio. There were no differences in plasma ptau181 levels between the sexes. There was no association between plasma ptau181 levels with age, years of education, MoCA, or functional assessment measured with CDR.

Conclusions

Plasma ptau181 levels help to identify LBD patients with amyloid-β co-pathology and are associated with AD CSF biomarkers, even at the prodromal MCI stage. These findings support the use of plasma ptau181 as a screening tool for amyloid-β co-pathology in LBD.

Aims

Plasma phosphorylated tau181 (ptau181) levels are been associated with amyloid-β deposition in Alzheimer’s disease (AD). Lewy body disease (LBD) frequently presents with amyloid-β co-pathology, which influences disease progression, cognitive decline, and brain atrophy.

We aimed to evaluate whether plasma ptau181 helps to identify amyloid-β co-pathology in the LBD spectrum, and whether plasma ptau181 levels in LBD are associated with AD cerebrospinal fluid (CSF) biomarkers.

Methods

We selected 203 Stanford research participants: 97 healthy controls, 37 Parkinson’s disease with normal cognition, 39 on the LBD-spectrum (25 MCI-LB and 14 dementia-LB), and 30 on the AD-spectrum (10 MCI-AD and 20 dementia-AD). Plasma ptau181 concentrations were measured using the Lumipulse G fully automated platform from Fujirebio Diagnostics. Diagnostic accuracy was evaluated with area-under-the-curve (AUC) values from receiver-operating characteristic (ROC) analyses.

Results

Plasma ptau181 levels predicted amyloid-β positivity in LBD patients (AUC=0.726). Combining plasma ptau181 levels with age, sex, years of education, APOE e4 genotype, and global cognition (MoCA), improved the prediction of amyloid-β positivity (AUC= 0.881). Similarly, plasma ptau181 levels predicted amyloid-β positivity in MCI-LB patients (AUC=0.691). This model was improved by including age, sex, years of education, APOE E4 genotype, and MoCA (AUC=0.826).

Plasma ptau181 levels were negatively associated with CSF Aβ42/Aβ40 ratio and positively associated with CSF ptau181/Aβ40 ratio. There were no differences in plasma ptau181 levels between the sexes. There was no association between plasma ptau181 levels with age, years of education, MoCA, or functional assessment measured with CDR.

Conclusions

Plasma ptau181 levels help to identify LBD patients with amyloid-β co-pathology and are associated with AD CSF biomarkers, even at the prodromal MCI stage. These findings support the use of plasma ptau181 as a screening tool for amyloid-β co-pathology in LBD.