Biomarkers.

Area of Science:

• Neuroscience
• Biomarker Discovery
• Alzheimer's Disease Research

Background:

• Identifying reliable biomarkers is crucial for staging neurodegeneration and cognitive impairment in Alzheimer's Disease (AD).
• Current methods require sensitive markers to track disease progression and inform therapeutic strategies.

Purpose of the Study:

• To investigate the association of cerebrospinal fluid (CSF) levels of NPTX1 and NPTXR with cognitive function, brain structure, and decline in the AD continuum.
• To evaluate the predictive power of NPTX1 and NPTXR for progression from mild cognitive impairment (MCI) to dementia.

Main Methods:

• 435 participants from the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort were analyzed.
• CSF levels of NPTX1 and NPTXR were measured and correlated with cognitive scores, cortical thickness, and brain atrophy over a median follow-up of 21 months.
• The ability of NPTX1 and NPTXR to differentiate progressive MCI was assessed.

Main Results:

• Lower CSF NPTX1 and NPTXR levels correlated with more severe cognitive impairment and faster rates of brain atrophy and cognitive decline in the AD continuum.
• NPTX1 and NPTXR were positively associated with cortical thickness, especially in individuals with amyloid-beta (Aβ) pathology.
• Baseline CSF NPTXR and NPTX1 levels effectively predicted progression to dementia in MCI participants within 3 years.

Conclusions:

• CSF NPTX1 and NPTXR show promise as biomarkers for staging neurodegeneration and cognitive dysfunction in the AD continuum.
• These biomarkers can provide insights for personalized therapeutic interventions and optimizing clinical trials.
• NPTX1 and NPTXR may aid in identifying individuals at higher risk of progressing to dementia.