P-tau Concentrations Research Articles

Tau and p-tau as CSF biomarkers in dementia: a meta-analysis

To evaluate the value of total tau (tau) and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) in the differential diagnosis of dementia, more specifically: dementia with Lewy Bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD), and Creutzfeldt-Jacob disease (CJD). A systematic literature search was performed to identify studies on tau and p-tau in DLB, FTLD, VaD and CJD. Tau concentrations were compared to healthy controls and to subjects with Alzheimer's disease (AD) using random effect meta-analysis. Outcome measures were Cohen's delta, sensitivity and specificity. Compared to controls, tau concentrations are moderately elevated in DLB, FTLD and VaD, while p-tau concentrations are only slightly elevated in DLB and not elevated in FTLD and VaD. Compared to AD, lower tau concentrations differentiated DLB with a sensitivity of 73% and a specificity of 90%, FTLD with sensitivity and specificity of 74%, and VaD with a sensitivity of 73% and a specificity of 86%. Relative to AD, lower p-tau values differentiated FTLD with a sensitivity of 79% and specificity of 83%, and VaD with a sensitivity of 88% and a specificity of 78%. CJD is characterized by extremely elevated tau concentrations with a sensitivity of 91% and a specificity of 98% vs. AD. CSF tau concentrations in DLB, FTLD and VaD are intermediate between controls and AD patients. Overlap with both controls and AD patients results in insufficient diagnostic accuracy, and the development of more specific biomarkers for these disorders is needed. CJD is characterized by extremely increased tau values, resulting in a sensitivity and specificity that exceeds 90%.

Deposition of Hyperphosphorylated Tau in Cerebellum of PS1 E280A Alzheimer's Disease

Early-onset familial Alzheimer's disease (AD) caused by presenilin-1 mutation E280A (PS1-E280A) presents wide clinical and neuropathological variabilities. We characterized clinically and neuropathologically PS1-E280A focusing in cerebellar involvement and compared it with early-onset sporadic Alzheimer's disease (EOSAD). Twelve E280A brains and 12 matched EOSAD brains were analyzed for beta-amyloid and hyperphosphorylated tau (pTau) morphology, beta-amyloid subspecies 1-40, 1-42 levels, pTau levels, and expression of stress kinases in frontal cortex and cerebellum. The data were correlated to clinical and genetic findings. We observed higher beta-amyloid load, beta-amyloid 1-42 and pTau concentrations in frontal cortex of PS1-E280A compared with EOSAD. High beta-amyloid load was found in the cerebellum of PS1-E280A and EOSAD patients. In PS1-E280A, beta-amyloid localized to the molecular and Purkinje cell layers, whereas EOSAD showed them in Purkinje and granular cell layers. Surprisingly, 11 out of 12 PS1-E280A patients showed deposition of pTau in the cerebellum. Also, seven out of 12 PS1-E280A patients presented cerebellar ataxia. We conclude that deposition of beta-amyloid in the cerebellum is prominent in early-onset AD irrespective of genetic or sporadic origin. The presence of pTau in cerebellum in PS1-E280A underscores the relevance of cerebellar involvement in AD and might be correlated to clinical phenotype.

Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is still challenging. Alzheimer's disease (AD), along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF) biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD). A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau181, Aβ42, NFL, TNF-α, TGFβ1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result—that is, their gait symptoms improved; 9 patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-α concentration was low in iNPH patients.

Cerebrospinal Fluid Markers for Alzheimer's Disease over the Lifespan: Effects of Age and the APOEε4 Genotype

In Alzheimer's disease (AD), the cerebral pathological changes begin many years before the clinical manifestation of the disease. Biomarkers for AD, such as the cerebrospinal fluid (CSF) concentrations of amyloid-β1-42 (Aβ1-42) and tau phosphorylated at threonine 181 (pTau181), may reflect these cerebral changes relatively early. Accordingly, cognitively healthy subjects at risk for AD often have altered CSF concentrations of Aβ1-42 and pTau181. In this study, we assessed the effects and interaction of two strong risk factors for AD, aging and the presence of the APOEε4 allele, on the CSF Aβ1-42 and pTau181 concentrations in 280 adults with normal cognition across the lifespan. For comparison, we further included 152 patients with probable AD. We found significant effects of age on the CSF Aβ1-42 and pTau181, and of the APOEε4 genotype on the Aβ1-42 levels in the cognitively normal participants. Carrying the APOEε4 allele was associated with a significant decrease of the Aβ1-42 concentrations in middle-aged and older participants. In the group of participants with AD, the Aβ1-42 levels were significantly lower in the APOEε4 carriers compared to the non-carriers. These findings demonstrate significant age effects on the CSF Aβ1-42 and pTau181 across lifespan. They also suggest that the decrease of Aβ1-42, but not the increase of pTau181 CSF levels is accelerated by the APOEε4 genotype in middle-aged and older adults with normal cognition.

Alzheimer's CSF markers in older schizophrenia patients

Cognitive impairment is prevalent in older schizophrenia patients but its biological basis is unknown. Neuropathological studies have not revealed Alzheimer disease (AD) lesion burden but in vivo data are lacking. We investigated the concentrations of CSF biomarkers of brain amyloidosis (Abeta42) and neurodegeneration (total and p-tau) in a group of older schizophrenia patients and related them to cognitive and MRI measures. Older schizophrenia (n = 11), AD patients (n = 20) and elderly controls (n = 6) underwent cognitive testing, lumbar puncture, and MRI scanning. Abeta42 and total and p-tau concentrations were assayed in the CSF. MRI volumes were assessed using both voxel-based (cortical pattern matching) and region-of-interest analyses. CSF tau concentration in older schizophrenia patients was within normal limits (total tau 171 ± 51 pg/ml, p-tau 32 ± 8 pg/ml), while CSF Abeta42 (465 ± 112 pg/ml) levels were significantly lower compared to healthy elders (638 ± 130 pg/ml) but higher than in AD patients (352 ± 76 pg/ml). There was a strong positive relationship between CSF total or p-tau levels and MMSE scores in schizophrenia patients but not in AD, where higher concentrations of total tau were correlated with higher volumes in the occipital cortex (r = 0.63, p = 0.036), while in AD a significant correlation was found between lower Abeta42 concentrations and lower gray matter volume in the cingulate and lateral orbital cortices (r > 0.46, p < 0.05). Older schizophrenia patients show a peculiar pattern of CSF Abeta42 and tau concentrations that relates to cognitive and structural markers but is not consistent with neurodegeneration and could be secondary to neurodevelopmental or drug treatment effects.

Cerebrospinal fluid tau and phosphorylated tau protein are elevated in corticobasal syndrome

Differentiating corticobasal syndrome (CBS) from progressive supranuclear palsy (PSP) and idiopathic Parkinson's disease (PD) can be difficult. To investigate the additional value of cerebrospinal fluid (CSF) biomarkers in the diagnostic differentiation of parkinsonism, we analyzed the CSF concentrations of total protein, lactate and brain specific proteins amyloid-β(42) protein, tau protein (t-tau), and tau protein phosphorylated at Thr181 (p-tau), in CSF samples from patients with PSP (n = 21), CBS (n = 12), and PD (n = 28). CBS patients demonstrated higher concentrations of t-tau and p-tau compared with PSP and PD patients. In discriminating CBS and PD, t-tau offered the best combination of sensitivity (75%) and specificity (90.9%), followed by p-tau (sensitivity 87.5% and specificity 75%). The p-tau/t-tau ratio resulted in sensitivity of 84.2% and specificity of 66.7% in discriminating PSP and CBS. In conclusion, our results suggest that CSF parameters are of additional value in the diagnostic differentiation of CBS and PD.

Cerebrospinal Fluid Tau and Amyloid β Proteins Do Not Correlate With Cognitive Functioning in Cognitively Impaired Memory Clinic Patients

ABSTRACTObjective: The aim of this study was to investigate the influence of cerebrospinal fluid (CSF), amyloid β42(Aβ42), phosphorylated tau181 (p-tau), and total tau (t-tau) on cognitive functioning.Methods: We analyzed the ability of the CSF biomarkers Aβ42, p-tau, and t-tau to predict the results on the Cambridge Cognitive Examination–Revised (CAMCOG-R), a cognitive screening test that assesses multiple cognitive domains, in 65 memory clinic patients (73.1±8.2 years) (n=30 probable Alzheimer's disease [AD], n=7 possible AD, n=12 non-AD dementia, n=16 mild cognitive impairment).Results: We found no correlations between CSF biomarkers and CAMCOG-R performance in the whole group, nor in subgroups based on aberrant biomarker concentrations.Discussion: Changed concentrations of CSF amyloid β42, p-tau, and t-tau cannot be directly linked to cognitive function in our sample of patients with cognitive impairment. Possibly, compensatory mechanisms such as cognitive reserve determine cognitive performance, rather than the absolute amount of damage caused by Aβ deposition and tangle formation. In addition, abnormal CSF biomarker concentrations may not be a direct reflection of the amount of neuronal damage, but merely serve as an indicator of AD pathology.Conclusion: While CSF biomarkers are valuable in establishing AD pathology, they cannot be used to predict severity of cognitive impairment.

Cerebrospinal Fluid Abnormalities and Rate of Decline in Everyday Function Across the Dementia Spectrum

To investigate the effect of cerebrospinal fluid (CSF) abnormalities on the rate of decline in everyday function in normal aging, mild cognitive impairment (MCI), and mild Alzheimer disease (AD). Immunoassays of total tau (t-tau), tau phosphorylated at threonine 181 (p-tau(181)), and beta-amyloid 1-42 (Abeta(42)) concentrations were performed in CSF obtained from participants in the Alzheimer's Disease Neuroimaging Initiative. Random effects regressions were used to examine the relationship among CSF abnormalities, cognitive impairment (assessed with the Alzheimer Disease Assessment Scale-cognitive subscale [ADAS-Cog]), and functional decline (assessed with the Pfeffer Functional Activities Questionnaire) and to determine whether the impact of CSF abnormalities on functional decline is mediated by cognitive impairment. Fifty-eight sites in the United States and Canada. One hundred fourteen cognitively intact adults, 195 patients with MCI, and 100 patients with mild AD. Main Outcome Measure Decline in the Pfeffer Functional Activities Questionnaire score. Abnormalities in all CSF analytes were associated with functional decline in MCI, and all but the t-tau:Abeta(42) ratio were associated with functional decline in controls. No abnormal CSF analyte was associated with functional decline in AD. Among controls, p-tau(181) concentration was the most sensitive to functional decline, whereas in MCI it was Abeta(42) concentration. Cerebrospinal fluid biomarkers were uniformly more sensitive to functional decline than the ADAS-Cog score among controls and variably so in MCI, whereas the ADAS-Cog score was unequivocally more sensitive than CSF biomarkers in AD. The impact of CSF abnormalities on functional decline in MCI was partially mediated by their effect on cognitive status. Across all diagnostic groups, persons with both tau and Abeta(42) abnormalities exhibited the steepest rate of functional decline. Abnormalities in CSF are associated with functional decline and thus with future development of AD in controls and patients with MCI. However, they do not predict further functional degradation in patients with AD. Persons with comorbid tau and Abeta(42) abnormalities are at greatest risk of functional loss.

Brain perfusion SPECT correlates with CSF biomarkers in Alzheimer’s disease

Our aim was to study the correlations between cerebrospinal fluid (CSF) biomarker levels such as beta-amyloid 42 (Abeta(42)), total and phosphorylated tau protein (T-tau and P-tau) and brain perfusion SPECT in Alzheimer's disease (AD) using a voxel-based methodology. Patients (n = 31) with clinical features of AD (n = 25) or amnestic mild cognitive impairment (aMCI) (n = 6) were retrospectively included. All subjects underwent the same clinical, neuropsychological and neuroimaging tests. They had a lumbar puncture and a brain perfusion ((99m)Tc-ECD) SPECT within a time interval of 10 (+/-26) days. Correlations between CSF biomarker concentrations and perfusion were studied using SPM2 software. Individual normalised regional activity values were extracted from the eligible clusters for calculation of correlation coefficients. No significant correlation was found between Abeta(42) concentrations and brain perfusion. A significant correlation (p < 0.01, corrected) was found between T-tau or P-tau concentrations and perfusion in the left parietal cortex. Our results suggest a strong correlation between T-tau and P-tau levels and decreased brain perfusion in regions typically affected by neuropathological changes in AD.

Association of CSF total tau and phospho-tau (181) with cerebral atrophy in mild cognitive impairment and Alzheimer's disease

Objective: To examine the association of levels of total tau (t-tau) and phospho-tau (p-tau) 181 with brain morphology in mild cognitive impairment as defined by the concept of aging-associated cognitive decline (AACD) and Alzheimer's disease (AD). Method: Twenty-three subjects with AACD, 16 with AD and 15 healthy controls underwent magnetic resonance imaging and lumbar puncture. Voxel-based morphometry (VBM) was performed to investigate the association between CSF tau levels and cerebral gray matter density throughout the entire brain. Results: VBM revealed both, elevated t-tau and p-tau181 concentrations to be associated with reduced gray matter density in temporal, parietal and frontal regions. Within the AACD group, elevated CSF levels of p-tau181 (but not t-tau) were correlated with a pronounced atrophy in the right hippocampus. Conclusion: Elevated CSF levels of t-tau and p-tau181 reflect degenerative processes in AD typical cortical regions. Our findings in AACD subjects support the hypothesis that p-tau181 might be more specifically related to neurodegenerative changes in early AD.

Biological markers in cerebrospinal fluid (CSF) and evaluation of in vitro effect of CSF on PC12 cell line viability in Alzheimer's disease

The definite diagnosis of Alzheimer's disease (AD) is based on post mortem pathological examination. To date, there is no laboratory test that can discriminate AD patients from healthy individuals. In the perspective of recent knowledge, there are three cerebrospinal fluid (CSF) markers which have the highest sensitivity and specificity: A beta(1-40), A beta(1-42), and p-tau. In the present study, 15 'Probable Alzheimer's Disease' (PAD) patients and 15 control subjects were included. PAD patients were selected from the patients of Dokuz Eylül University Neurology Department Dementia outpatient clinic and control subjects were selected from the patients who were undergone epidural anesthesia because of any surgical operation. The concentrations of Ab1-40, Ab1-42, and p-tau in CSF were quantified by using ELISA. Also, the effects of 'PAD patients' CSF on the survival of PC12 cell line were assessed. There was a significant decrease of Ab1-40 and increase of p-tau in patients with AD when compared with controls. Ab1-42 concentration was not significantly different between groups. There was a positive correlation between duration of the disease and CSF of p-tau concentration in patients with AD. There was no significant difference in cell line viability values between groups.

Preclinical Evidence of Alzheimer Changes

Alterations in cerebrospinal fluid (CSF) tau and beta-amyloid peptide 1-42 (Abeta(42)) levels and rates of cerebral glucose metabolism (CMRglu) on fluorodeoxyglucose positron emission tomography (FDG-PET) occur years before clinical symptoms of Alzheimer disease (AD) become manifest, but their relationship remains unclear. To determine whether CSF AD biomarker levels and CMRglu in healthy individuals correlate in brain structures affected early in AD. Cohort study. Alzheimer disease research center. Twenty individuals without dementia aged 46 to 83 years. Lumbar CSF sampling and FDG-PET imaging of CMRglu. The CSF Abeta(42), tau, and tau phosphorylated at threonine 181 (ptau(181)) levels were measured using immunobead-based multiplex assays. Correlations between CMRglu and CSF biomarker levels were analyzed via voxel-based and volume-of-interest approaches. Voxel-based analyses demonstrated significant negative correlations between CSF tau and ptau(181) levels and CMRglu in the posterior cingulate, precuneus, and parahippocampal regions. In contrast, a limited positive correlation was found between CSF Abeta(42) levels and CMRglu in the inferior temporal cortex. Volume-of-interest analyses confirmed negative associations between CSF tau and ptau(181) levels and CMRglu in the parietal and medial parietal lobes and a positive association between CSF Abeta(42) levels and CMRglu in the parahippocampal gyrus. In healthy individuals, higher CSF tau and ptau(181) concentrations were associated with more severe hypometabolism in several brain regions affected very early in AD, whereas lower CSF Abeta(42) concentrations were associated with hypometabolism only in the medial temporal lobe. This suggests that early tau and Abeta abnormalities may be associated with subtle synaptic changes in brain regions vulnerable to AD. A longitudinal assessment of CSF and FDG-PET biomarkers is needed to determine whether these changes predict cognitive impairment and incipient AD.

Added diagnostic value of CSF biomarkers in differential dementia diagnosis

This study aimed to investigate whether cerebrospinal fluid (CSF) biomarkers could have helped the clinician in differential dementia diagnosis in case of clinically ambiguous diagnoses, as compared to autopsy-confirmed dementia diagnosis as gold standard. Twenty-two patients of our autopsy-confirmed dementia population totalling 157 patients had an ambiguous clinical diagnosis at CSF sampling and were included in statistical analysis. CSF levels of β-amyloid peptide (Aβ(1-42)), total tau protein (T-tau) and tau phosphorylated at threonine 181 (P-tau(181P)) were determined. A biomarker-based model was applied to discriminate between AD and NON-AD dementias. AD and NON-AD patients showed no significant differences in Aβ(1-42) and T-tau concentrations, whereas P-tau(181P) concentrations were significantly higher in AD compared to NON-AD patients. The biomarker-based diagnostic model correctly classified 18 of 22 (82%) patients with clinically ambiguous diagnoses. Using a biomarker-based model in patients with clinically ambiguous diagnoses, a correct diagnosis would have been established in the majority of autopsy-confirmed AD and NON-AD cases, indicating that biomarkers have an added diagnostic value in cases with ambiguous clinical diagnoses.

Neuropsychiatric Correlates of Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease

Background: The aim of this study was to explore the relationship between cerebrospinal fluid biomarkers and neuropsychiatric symptoms in people with Alzheimer’s disease. Psychosis, agitation, apathy and depression were assessed using standardised measures in 32 patients with mild Alzheimer’s disease. Methods: The levels of the 42-amino-acid form of β-amyloid (Aβ_1–42), tau and p-tau (phosphorylated at threonine 181) were quantified using the conventional enzyme-linked immunosorbent assay method. Results: Our result shows that apathy is significantly correlated with tau and p-tau but not with Aβ_1–42. There were no significant correlations between indices of psychosis/agitation,or depression and cerebrospinal fluid Aβ_1–42, tau or p-tau concentrations. Conclusion: Our finding suggests that apathy is associated with the level of neurofibrillary tangles in people with mild Alzheimer’s disease. In contrast, the overall levels of neurofibrillary tangles or amyloid plaques do not seem to be associated with depression or psychosis, indicating that other brain changes contribute to these symptoms.

The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's disease

While cerebrospinal fluid (CSF) biomarkers are of use in the prediction and diagnosis of Alzheimer's disease our understanding of the background effects of age and the ApoE genotype is limited. Seventy-eight community-based normal volunteers (mean age 60 ± 10 years, range 36–86) were examined to determine the relationships between CSF measures of total tau (T-tau), hyperphosphorylated tau (P-tau 231), amyloid beta (Aβ42/Aβ40 ratio), and isoprostane (IP) with age and ApoE genotype. The results showed that age by ɛ4 genotype interactions were found for P-tau231 ( β = 1.82; p < 0.05) and IP ( β = 1.6; p < 0.05). T-tau CSF concentration increased with age. The increasing CSF concentrations of P-tau and IP in ɛ4 carriers suggest that early tauopathy and oxidative stress may be related to the increased risk for AD. The data also suggest that T-tau changes are more age dependent than Aβ changes. The evidence that P-tau231 and IP are the earliest markers for the neuronal damage related to AD awaits longitudinal study.

Longitudinal stability of CSF biomarkers in Alzheimer's disease

Biomarker levels in cerebrospinal fluid (CSF) may serve as surrogate markers for treatment efficacy in clinical trials of disease-modifying drugs against Alzheimer's disease (AD). A prerequisite, however, is that the marker is sufficiently stable over time in individual patients. Here, we tested the stability of the three established CSF biomarkers for AD, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau 181) and the 42 amino acid isoform of β-amyloid (Aβ42), over 6 months in a cohort of AD patients on stable treatment with acetylcholinesterase (AChE) inhibitors. Fifty-three patients completed the study, 29 men and 24 women, mean age (±S.D.) 76.1 ± 7.9 years. Mean levels of CSF biomarkers were very stable between baseline and endpoint, with coefficients of variation (CVs) of 4.4–6.1%. Intra-individual biomarker levels at baseline and endpoint were also highly correlated with Pearson r-values above 0.95 ( p < 0.0001), for all three markers. We conclude that T-tau, P-tau and Aβ42 concentrations in CSF are remarkably stable over a 6-month period in individual AD patients. This suggest that these biomarkers may have a potential to identify and monitor very minor biochemical changes induced by treatment, and thus support their possible usefulness as surrogate markers in clinical trials with drug candidates with disease-modifying potential, such as secretase inhibitors, Aβ immunotherapy and tau phosphorylation inhibitors.

Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study

Disease-modifying treatment strategies for Alzheimer's disease have led to an urgent need for biomarkers to identify the disease at a very early stage. Here, we assess the association between CSF biomarkers and incipient Alzheimer's in patients with mild cognitive impairment (MCI). From a series of 180 consecutive patients with MCI, we assessed 137 who underwent successful lumbar puncture at baseline. Patients at risk of developing dementia were followed clinically for 4-6 years. Additionally, 39 healthy individuals, cognitively stable over 3 years, served as controls. We analysed CSF concentrations of beta amyloid(1-42) (Abeta42), total tau (T-tau), and phosphorylated tau (P-tau181) using Luminex xMAP technology. During follow-up, 57 (42%) patients with MCI developed Alzheimer's disease, 21 (15%) developed other forms of dementia, and 56 (41%) remained cognitively stable for 5.2 years (range 4.0-6.8). A combination of CSF T-tau and Abeta42 at baseline yielded a sensitivity of 95% and a specificity of 83% for detection of incipient AD in patients with MCI. The relative risk of progression to Alzheimer's disease was substantially increased in patients with MCI who had pathological concentrations of T-tau and Abeta42 at baseline (hazard ratio 17.7, p<0.0001). The association between pathological CSF and progression to Alzheimer's disease was much stronger than, and independent of, established risk factors including age, sex, education, APOE genotype, and plasma homocysteine. The combination of T-tau and Abeta42/P-tau181 ratio yielded closely similar results (sensitivity 95%, specificity 87%, hazard ratio 19.8). Concentrations of T-tau, P-tau181, and Abeta42 in CSF are strongly associated with future development of Alzheimer's disease in patients with MCI.

CSF amyloid β42 and tau levels correlate with AIDS dementia complex

There is concern that AIDS dementia complex (ADC) may be complicated by Alzheimer disease (AD). Because AD presence and risk are related to CSF beta-amyloid(1-42) (Abeta42), total tau (t-tau), and phosphorylated tau (p-tau), the authors examined these in ADC, AD, and controls. ADC had significantly decreased CSF Abeta42 and increased t-tau and p-tau concentrations similar to AD, suggesting that ADC may be associated with AD or an AD-like process.

Differentiation of Geriatric Major Depression From Alzheimer’s Disease With CSF Tau Protein Phosphorylated at Threonine 231

Differentiation of geriatric major depression from Alzheimer's disease is hampered by overlapping symptoms. Increased CSF concentrations of tau protein phosphorylated at threonine 231 (p-tau(231)) have been suggested as a biomarker for Alzheimer's disease. The authors asked whether p-tau(231) levels improve the differential diagnosis between geriatric major depression and Alzheimer's disease. Included were 34 depression subjects, 64 with probable Alzheimer's disease, 17 with possible Alzheimer's disease, and 21 healthy comparison subjects. P-tau(231) concentrations were measured with an enzyme-linked immunosorbent assay. P-tau(231) levels were significantly higher in Alzheimer's disease than in geriatric major depression patients and healthy comparison subjects. For differentiation of probable Alzheimer's disease from major depression, p-tau(231) correctly allocated 87% of subjects. When possible mild Alzheimer's disease was compared to major depression, p-tau(231) correctly allocated 78% of subjects. CSF p-tau(231) should be evaluated as a potential biological marker for differentiation of geriatric depression from Alzheimer's disease.