Serum Amyloid P Component as a Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease

Abstract

Background: Serum amyloid P component (SAP), present in amyloid-β (Aβ) plaques in Alzheimer’s disease (AD), may protect Aβ deposits against proteolysis, thereby promoting plaque formation. The aim was to investigate if SAP levels in cerebrospinal fluid (CSF) and serum can be used to discriminate controls, AD and mild cognitive impairment (MCI) patients, and to identify incipient AD among MCI patients. Methods: SAP levels in CSF and serum were determined in 30 controls, 67 MCI and 144 AD patients. At follow-up, 39 MCI patients had progressed to dementia, while 25 had remained stable (mean follow-up time: 2.6 ± 1.0 and 2.1 ± 0.8 years). Results: Cross-sectionally no differences were found in SAP levels in CSF and serum between the groups. MCI patients that had progressed to dementia at follow-up had lower CSF SAP levels (13 mg/l, range 3.3–199.3 mg/l) than MCI nonprogressors (20.2 mg/l, range 7.0–127.7 mg/l; p < 0.05). A low CSF SAP level was associated with a 2-fold increased risk of progression to AD (hazard ratio = 2.2; 95% confidence interval = 0.9–5.4). Conclusion: Our data suggest that measurement of CSF SAP levels can aid in the identification of incipient AD among MCI patients.

Brain Serum Amyloid P Levels are Reduced in Individuals that Lack Dementia While Having Alzheimer’s Disease Neuropathology

“…SAP does not readily cross the blood brain barrier; however, neurons in the brain can produce SAP, and this production is upregulated in AD brains [8] although there is no difference in the cerebrospinal fluid (CSF) levels of SAP between AD patients and age-matched normal controls [9–11]. Among AD patients, one study using 70 patients found that higher CSF levels of SAP tended to correlate with less dementia (9), while a smaller study using 20 patients did not observe any trend (10).…”

Efflux transport of serum amyloid P component at the blood-brain barrier

“…This effl ux mechanism can explain the very low CSF index values for SAP observed by Mulder et al [37]. However, the reduction of CSF SAP levels found in demented AD brains may also suggest that SAP located in brain interstitial fl uid is quickly deposited to amyloid plaques [34,36,37].…”

“…However, no signifi cant increase in SAP production could be detected in postmortem samples from hippocampus and frontal cortex of nondemented subjects with AD neuropathology [32]. Available data about SAP levels in cerebrospinal fl uid (CSF) of AD patients are controversial: a study showed elevated SAP concentration [33], whereas the others [34][35][36][37] did not detect signifi cant differences between AD and age-matched control patients. However, CSF SAP level correlated with cognitive function measured by Mini-Mental State Examination [34], and a low value was associated with two-fold increased risk of progression to AD in case of mild cognitive impairment patients [36].…”

“…Available data about SAP levels in cerebrospinal fl uid (CSF) of AD patients are controversial: a study showed elevated SAP concentration [33], whereas the others [34][35][36][37] did not detect signifi cant differences between AD and age-matched control patients. However, CSF SAP level correlated with cognitive function measured by Mini-Mental State Examination [34], and a low value was associated with two-fold increased risk of progression to AD in case of mild cognitive impairment patients [36]. Interestingly, increased local SAP synthesis in the brain of AD patients did not substantially contribute to the CSF levels, probably because of deposition in amyloid plaques [37].…”

New Frontiers in Alzheimer's Disease Diagnosis

“…In addition, the major acute-phase protein SAP (Serum amyloid P component) has lower levels in MCI patients who progressed to AD than in those who did not progress to AD [164], suggesting that low SAP levels are linked to an increased risk of progression to AD.…”