CONTEXT: Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease. OBJECTIVES: To assess the ability of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42) to predict future development of AD dementia within 9.2 years in patients with mild cognitive impairment (MCI) and to compare CSF biomarkers between early and late converters to AD. DESIGN: A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years). SETTING: Memory disorder clinic. Patients A total of 137 patients with MCI who underwent lumbar puncture at baseline. MAIN OUTCOME MEASURE Conversion to AD dementia. RESULTS: During follow-up, 72 patients (53.7%) developed AD and 21 (15.7%) progressed to other forms of dementia. At baseline, CSF Aβ42 levels were reduced and T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with nonconverters (P < .001). Baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted to AD within 0 to 5 years (early converters) compared with those who converted between 5 and 10 years (late converters). However, CSF T-tau and P-tau levels were significantly higher in early converters vs late converters. A baseline Aβ42:P-tau ratio predicted the development of AD within 9.2 years with a sensitivity of 88%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 86%. CONCLUSIONS: Approximately 90% of patients with MCI and pathologic CSF biomarker levels at baseline develop AD within 9 to 10 years. Levels of Aβ42 are already fully decreased at least 5 to 10 years before conversion to AD dementia, whereas T-tau and P-tau seem to be later markers. These results provide direct support in humans for the hypothesis that altered Aβ metabolism precedes tau-related pathology and neuronal degeneration.
CONTEXT: Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease. OBJECTIVES: To assess the ability of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42) to predict future development of AD dementia within 9.2 years in patients with mild cognitive impairment (MCI) and to compare CSF biomarkers between early and late converters to AD. DESIGN: A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years). SETTING:Memory disorder clinic. Patients A total of 137 patients with MCI who underwent lumbar puncture at baseline. MAIN OUTCOME MEASURE Conversion to AD dementia. RESULTS: During follow-up, 72 patients (53.7%) developed AD and 21 (15.7%) progressed to other forms of dementia. At baseline, CSF Aβ42 levels were reduced and T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with nonconverters (P < .001). Baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted to AD within 0 to 5 years (early converters) compared with those who converted between 5 and 10 years (late converters). However, CSF T-tau and P-tau levels were significantly higher in early converters vs late converters. A baseline Aβ42:P-tau ratio predicted the development of AD within 9.2 years with a sensitivity of 88%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 86%. CONCLUSIONS: Approximately 90% of patients with MCI and pathologic CSF biomarker levels at baseline develop AD within 9 to 10 years. Levels of Aβ42 are already fully decreased at least 5 to 10 years before conversion to AD dementia, whereas T-tau and P-tau seem to be later markers. These results provide direct support in humans for the hypothesis that altered Aβ metabolism precedes tau-related pathology and neuronal degeneration.
Authors: Ann Hake; Paula T Trzepacz; Shufang Wang; Peng Yu; Michael Case; Helen Hochstetler; Michael M Witte; Elisabeth K Degenhardt; Robert A Dean Journal: Alzheimers Dement Date: 2015-04-24 Impact factor: 21.566
Authors: Burcu F Darst; Rebecca L Koscik; Annie M Racine; Jennifer M Oh; Rachel A Krause; Cynthia M Carlsson; Henrik Zetterberg; Kaj Blennow; Bradley T Christian; Barbara B Bendlin; Ozioma C Okonkwo; Kirk J Hogan; Bruce P Hermann; Mark A Sager; Sanjay Asthana; Sterling C Johnson; Corinne D Engelman Journal: J Alzheimers Dis Date: 2017 Impact factor: 4.472
Authors: Mehdi Mirzaei; Kanishka Pushpitha; Liting Deng; Nitin Chitranshi; Veer Gupta; Rashi Rajput; Abu Bakr Mangani; Yogita Dheer; Angela Godinez; Matthew J McKay; Karthik Kamath; Dana Pascovici; Jemma X Wu; Ghasem Hosseini Salekdeh; Tim Karl; Paul A Haynes; Stuart L Graham; Vivek K Gupta Journal: Mol Neurobiol Date: 2019-02-01 Impact factor: 5.590