Sensitive quantitative assays for tau and phospho-tau in transgenic mouse models.

Transgenic mouse models have been an invaluable resource in elucidating the complex roles of β-amyloid and tau in Alzheimer's disease. Although many laboratories rely on qualitative or semiquantitative techniques when investigating tau pathology, we have developed 4 Low-Tau, Sandwich enzyme-linked immunosorbent assays (ELISAs) that quantitatively assess different epitopes of tau relevant to Alzheimer's disease: total tau, pSer-202, pThr-231, and pSer-396/404. In this study, after comparing our assays with commercially available ELISAs, we demonstrate our assay's high specificity and quantitative capabilities using brain homogenates from tau transgenic mice, htau, JNPL3, and tau knockout.

Magnetic resonance imaging improves cerebrospinal fluid biomarkers in the early detection of Alzheimer's disease.

Little is known of combined utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers for prediction of Alzheimer's disease (AD) and longitudinal data is scarce. We examined these biomarkers at baseline and longitudinally in incipient AD. Forty-five subjects [21 controls (NL-NL), 16 stable MCI (MCI-MCI), 8 MCI who declined to AD (MCI-AD)] received MRI and lumbar puncture at baseline and after 2 years.

Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment.

Objectives: To longitudinally evaluate five cerebrospinal fluid (CSF) biomarkers in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD).

Methods: A baseline and 2-year follow-up clinical and CSF study of 86 subjects, including 22 MCI patients that declined to AD (MCI-AD), 43 MCI that did not deteriorate (MCI-MCI) and 21 controls (NL-NL). All subjects were studied for total and phosphorylated tau (T-tau, P-tau(231)), amyloid beta (Abeta) Abeta(42)/Abeta(40) ratio, isoprostane (IP) as well as P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios.

Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints.

Background: We examined whether cerebral metabolic rates for glucose (CMRglc) on 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) and cerebrospinal fluid (CSF) markers of Alzheimer's disease (AD) are altered in cognitively normal apolipoprotein E (ApoE) E4 carriers with subjective memory complaints (SMC).

Methods: Twenty-eight middle-aged normal subjects (NL) were examined, including 13 E4 carriers (E4+; 6 with SMC [SMC+] and 7 without SMC [SMC-]) and 15 noncarriers (E4-; 7 SMC+ and 8 SMC-). Subjects received an FDG-PET scan and a lumbar puncture to measure CSF total (T-Tau) and hyperphosphorylated tau(231) (P-Tau), 40 and 42 amino acid forms of beta-amyloid (Abeta40 and Abeta42), and F(2)-isoprostane (IP).