Alzheimer's disease (AD) is the most common cause of
dementia, characterized by progressive
cognitive decline. The main disease hallmarks include
amyloid beta aggregates and neurofibrillary tangles. Brain pathology is reflected in cerebrospinal fluid (CSF); the core
biomarkers amyloid beta 1-42, total and phosphorylated
tau protein levels are changed, relative to cognitively normal elderly. Still, there is a need for additional
biomarkers which could identify disease more accurately and at an earlier stage, predict severity and be used in research settings. Here we evaluated 30 brain-related
proteins as candidate
biomarkers of AD.
Proteins were quantified in CSF samples from cognitively healthy individuals (n = 23) and patients with
mild cognitive impairment (MCI) due to AD (n = 20) or
dementia due to AD (n = 10) using selected reaction monitoring mass spectrometry assays. APLP1
protein was increased in MCI relative to control (p < 0.001). The best discrimination between MCI vs. controls was observed with a model combining APLP1 and SPP1
proteins (area under the curve, AUC = 0.84). The strongest associations between
protein abundance and disease severity were found for APLP1, CNTN2 and SPP1
proteins, which had a significant correlation with MMSE and CDR tests (p < 0.05). This study identifies new
proteins with
biomarker potential at various stages of AD severity.
SIGNIFICANCE: The current study evaluated 30 brain-related, highly specific
proteins as candidate
biomarkers of AD diagnosis.
Protein APLP1 showed promise as early AD
biomarker;
protein panel APLP1 and SPP1 had the best diagnostic potential in discriminating MCI from control group, while
proteins APLP1, SPP1 and CNTN2 may be indicators of
disease progression, demonstrating weak to moderate correlation with cognitive tests. This study therefore identifies new
proteins with
biomarker potential at early AD stage. If the performance of proposed
biomarkers is further confirmed, these
proteins may add value in the clinic or clinical trial settings as diagnostic
biomarkers (alone or in combination with the existing
biomarkers) of the prodromal AD stage, and in monitoring
disease progression.