A 70-year-old man presents with a 2-year history of progressive memory loss, word-finding difficulty, and inability to manage finances. MMSE is 19/30. MRI shows hippocampal and medial temporal lobe atrophy. CSF shows decreased Abeta-42, increased total tau and phospho-tau. Which of the following biomarker patterns is MOST consistent with Alzheimer's disease?
- A Increased CSF Abeta-42, decreased tau
- B Normal CSF Abeta-42, increased alpha-synuclein
- C Decreased CSF Abeta-42, increased total tau and phospho-tau ✓
- D Decreased CSF Abeta-42, decreased tau
Correct answer: C. Decreased CSF Abeta-42, increased total tau and phospho-tau
Explanation
The AD CSF biomarker signature consists of: decreased Abeta-42 (due to amyloid deposition in plaques, reducing CSF levels), and increased total tau (neuronal injury marker) and phospho-tau-181 (a specific phosphorylation pattern of neurofibrillary tangles). This combination has high sensitivity and specificity for AD pathology. Elevated alpha-synuclein in CSF is associated with Parkinson's disease/DLB. The AT(N) biomarker framework categorizes: A=amyloid (Abeta-42), T=tau pathology (phospho-tau), N=neurodegeneration (total tau, MRI atrophy, FDG-PET).
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.