Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People

Abstract

To identify biomarker patterns typical for Alzheimer disease (AD) in an independent, unsupervised way, without using information on the clinical diagnosis.

CSF cutoffs for MCI due to AD depend on APOEε4 carrier status

“…External validation of the APOEε4 effect on CSF Aβ42/P-tau distribution was carried out in the independent dataset of ADNI, confirming the better fit of the model with 3 compared to the 2 components. Our findings are consistent with a previous study using mixture model on CSF Aβ42/P-tau ratio from the ADNI cohort (De Meyer et al, 2010) and showing the same robustness for the models with 2 and 3 components (AIC= 4138 and 4139, respectively). The uncertain definition of the intermediate subgroup in the unadjusted model of the above mentioned study is probably due to the higher number of normal subjects in the derivation cohort (114 rather than 76 as here) given that the APOEε4 effect on P-tau occurred in MCI but not in normal subjects (Risacher et al, 2013;Sunderland et al, 2004;Vemuri et al, 2010).…”

CSF cutoffs for MCI due to AD depend on APOEε4 carrier status

“…External validation of the APOEε4 effect on CSF Aβ42/P-tau distribution was carried out in the independent dataset of ADNI, confirming the better fit of the model with 3 compared to the 2 components. Our findings are consistent with a previous study using mixture model on CSF Aβ42/P-tau ratio from the ADNI cohort (De Meyer et al, 2010) and showing the same robustness for the models with 2 and 3 components (AIC= 4138 and 4139, respectively). The uncertain definition of the intermediate subgroup in the unadjusted model of the above mentioned study is probably due to the higher number of normal subjects in the derivation cohort (114 rather than 76 as here) given that the APOEε4 effect on P-tau occurred in MCI but not in normal subjects (Risacher et al, 2013;Sunderland et al, 2004;Vemuri et al, 2010).…”

Diagnostic Power of 24S-Hydroxycholesterol in Cerebrospinal Fluid: Candidate Marker of Brain Health

“…This is consistent with previous findings that about 20-25% of a healthy old population has some accumulation of amyloid in the brain as shown by PET [25]. An AD-like biomarker signature (decreased A␤ 42 , increased T-tau) was found in 36% of cognitive normal aging population [26].…”

Early Prediction of Alzheimer’s Disease Using Null Longitudinal Model-Based Classifiers

“…We found subjects clinically diagnosed as CN at baseline with abnormal CSF profile, which is consistent with previous studies where the presence of possible AD pathology has been found in ADNI control subjects [18, 51, 52]. These findings may be because ADNI subject diagnosis is made independently of the CSF biomarkers values (see S1 Appendix).…”

CSF cutoffs for MCI due to AD depend on APOEε4 carrier status

“…External validation of the APOEε4 effect on CSF Aβ42/P-tau distribution was carried out in the independent dataset of ADNI, confirming the better fit of the model with 3 compared to the 2 components. Our findings are consistent with a previous study using mixture model on CSF Aβ42/P-tau ratio from the ADNI cohort (De Meyer et al, 2010) and showing the same robustness for the models with 2 and 3 components (AIC= 4138 and 4139, respectively). The uncertain definition of the intermediate subgroup in the unadjusted model of the above mentioned study is probably due to the higher number of normal subjects in the derivation cohort (114 rather than 76 as here) given that the APOEε4 effect on P-tau occurred in MCI but not in normal subjects (Risacher et al, 2013;Sunderland et al, 2004;Vemuri et al, 2010).…”

Diagnostic Power of 24S-Hydroxycholesterol in Cerebrospinal Fluid: Candidate Marker of Brain Health

“…This is consistent with previous findings that about 20-25% of a healthy old population has some accumulation of amyloid in the brain as shown by PET [25]. An AD-like biomarker signature (decreased A␤ 42 , increased T-tau) was found in 36% of cognitive normal aging population [26].…”

Early Prediction of Alzheimer’s Disease Using Null Longitudinal Model-Based Classifiers

“…We found subjects clinically diagnosed as CN at baseline with abnormal CSF profile, which is consistent with previous studies where the presence of possible AD pathology has been found in ADNI control subjects [18, 51, 52]. These findings may be because ADNI subject diagnosis is made independently of the CSF biomarkers values (see S1 Appendix).…”

CSF cutoffs for MCI due to AD depend on APOEε4 carrier status

“…External validation of the APOEε4 effect on CSF Aβ42/P-tau distribution was carried out in the independent dataset of ADNI, confirming the better fit of the model with 3 compared to the 2 components. Our findings are consistent with a previous study using mixture model on CSF Aβ42/P-tau ratio from the ADNI cohort (De Meyer et al, 2010) and showing the same robustness for the models with 2 and 3 components (AIC= 4138 and 4139, respectively). The uncertain definition of the intermediate subgroup in the unadjusted model of the above mentioned study is probably due to the higher number of normal subjects in the derivation cohort (114 rather than 76 as here) given that the APOEε4 effect on P-tau occurred in MCI but not in normal subjects (Risacher et al, 2013;Sunderland et al, 2004;Vemuri et al, 2010).…”

Diagnostic Power of 24S-Hydroxycholesterol in Cerebrospinal Fluid: Candidate Marker of Brain Health

“…This is consistent with previous findings that about 20-25% of a healthy old population has some accumulation of amyloid in the brain as shown by PET [25]. An AD-like biomarker signature (decreased A␤ 42 , increased T-tau) was found in 36% of cognitive normal aging population [26].…”

Early Prediction of Alzheimer’s Disease Using Null Longitudinal Model-Based Classifiers

“…We found subjects clinically diagnosed as CN at baseline with abnormal CSF profile, which is consistent with previous studies where the presence of possible AD pathology has been found in ADNI control subjects [18, 51, 52]. These findings may be because ADNI subject diagnosis is made independently of the CSF biomarkers values (see S1 Appendix).…”