Your answer Was Incorrect
NEUROSAE 2018 ANNUAL MEETING EDITION (VOLUME 10, ISSUE 3)
QUESTION 48 OF 100
A 55-year-old woman presents with a primary complaint of changes in attention span. She denies memory issues, difficulty recalling names, speech problems, or difficulty with calculation. Results of her Mini-Mental State Examination and Montreal Cognitive Assessment are 30. The rest of the neurologic exam is unremarkable. She confirms her mother had Alzheimer’s dementia in her late 80’s and fears her symptoms are early signs of dementia. She also states she read an article about measuring biomarkers as a means of diagnosis. The patient is advised that the diagnosis is based on a clinical history and that biomarkers and imaging studies can assist in the diagnosis or assess her risk for dementia. She requests a lumbar puncture and asks for a definition of a positive result. Which of the following spinal biomarker results suggests a greater risk for Alzheimer’s dementia in this patient?
A. Low CSF Abeta 42, high phosphorylated tau
B. High CSF Abeta 42, high phosphorylated tau **
C. Normal CSF Abeta 42 and phosphorylated tau
D. High CSF Abeta 42, low phosphorylated tau
E. Low CSF Abeta 42, low phosphorylated tau
** = Your answer
The main pathology in the Alzheimer’s disease is neurofibrillary tangles composed of hyperphosphorylated tau and amyloid plaques composed of beta-amyloid fibrils. Measures of tau and Aβ42 in CSF have been identified as being the most promising, informative biomarkers as they reflect the molecular pathological hallmarks of Alzheimer’s disease. The processing of amyloid precursor protein results in two Aβ proteins Abeta 40 and Abeta 42. Abeta 40 is soluble and does not form plaques, whereas Abeta 42 is highly insoluble and contains amyloidogenic-forming plaques. Tau is a microtubule associated protein that stabilizes axonal microtubules. When tau gets abnormally hyperphosphorylated, it dissociates from microtubules and accumulates as neurofibrillary tangles. Individuals with Alzheimer’s disease have been shown to have lower CSF Abeta 42 compared with cognitively normal controls. Lower CSF levels of Abeta 42 in Alzheimer’s disease may represent increased incorporation of the CSF Abeta 42 into amyloid plaques. Both total tau and hyperphosphorylated tau in CSF appears to reflect neuronal and axonal degeneration and is correlated with the burden of neurofibrillary tangles in the brain. CSF tau has been shown to be elevated in patients with Alzheimers disease. The results for this patient are low CSF Abeta42, high phosphorylated tau. Assessment of biomarkers in CSF can be a sensitive test for diagnosis of Alzheimers disease in young patients who might not have all the clinical symptoms.
* Sperling R, Johnson K. Biomarkers of Alzheimer disease: current and future applications to diagnostic criteria. Continuum Lifelong Learning Neurol. 2013;19(2):325-338.