Serial CSF sampling in Alzheimer's disease: specific versus non-specific markers

Area of Science:

• Neurology
• Biochemistry
• Biomarker Research

Background:

• Alzheimer's disease (AD) diagnosis relies on clinical assessment and specific biomarkers.
• Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are crucial for understanding disease progression.

Purpose of the Study:

• To investigate longitudinal changes in CSF levels of various biomarkers in non-demented subjects, mild cognitive impairment (MCI), and AD patients.
• To identify biomarkers that change over time and correlate with disease progression and cognitive decline.

Main Methods:

• Longitudinal study design with two lumbar punctures (minimum 6 months apart) in 24 non-demented, 62 MCI, and 68 AD patients.
• Analysis of CSF levels of amyloid-beta 40/42 (Aβ40/42), total tau (tau), phosphorylated tau (ptau-181), isoprostane, neurofilaments heavy (NfH), and light (NfL).
• Linear mixed models used to assess changes over time and differences between diagnostic groups.

Main Results:

• AD-specific markers (Aβ42, tau, ptau-181) differentiated diagnostic groups but did not show significant changes over time.
• Nonspecific biomarkers (isoprostane, Aβ40, tau, NfL) exhibited changes over time; NfL decreased, while isoprostane, Aβ40, and tau increased.
• Isoprostane showed the most significant increase and was associated with MCI to AD progression and cognitive decline (MMSE scores).

Conclusions:

• Nonspecific CSF biomarkers, particularly isoprostane, demonstrate significant changes over time in individuals with cognitive impairment and AD.
• Isoprostane may serve as a valuable, dynamic biomarker for monitoring disease progression and cognitive decline in Alzheimer's disease.
• These findings suggest potential for using nonspecific biomarkers in longitudinal AD monitoring.