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CSF biomarkers in neuropathological Alzheimer's disease
Author(s) -
Leroy Melanie,
Maurage Claude Alain,
Pasquier Florence,
Deramecourt Vincent,
Lebouvier Thibaud
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.040217
Subject(s) - pathological , cerebrospinal fluid , medicine , lumbar puncture , disease , pathology , autopsy , memory clinic , dementia
Background Since the new ATN classification system positing a biological definition of Alzheimer’s disease (AD), cerebrospinal fluid (CSF) biomarkers are the keystone of AD diagnosis in countries where amyloid and tau positron emission tomography (PET) are not available. However, data confronting CSF biomarkers with pathology are still scarce. Method Among the 242 patients within Lille Brain bank, 23 patients had both CSF biomarkers and a neuropathologically confirmed AD. CSF collection was performed during follow up at the Lille Memory Clinic. CSF Ab 42 , Tau and pTau were measured and classified as pathological or normal regarding the cutoff at the time. The ATN profile (where A+ stands for pathological Ab 42 , T+ for pathological pTau and N+ for pathological Tau) was then determined. Result 21/23 patients had early onset AD, the age at first symptoms, the delay between the first symptoms and the lumbar puncture (LP) as well as the the delay between the autopsy and the LP were not different between groups. The MMSE at LP was above 15 in the A+T+N‐ (23.8 ± 4.5), the A‐T‐N+ (22) and the A+T+N+ group, and was statistically different between A+T+N‐ vs A‐T‐N+ (p = 0.03) and A+T+N‐ vs A‐T+N+ (P = 0.01) groups. Among our pathologically proved AD cases, 14/23 were A+T+N+, while 7 patients had 2 pathological biomarkers (4 were A+T+N‐ and 3 were A‐T+N+) and 2 patients had one (one was A+T‐N‐ and one was A‐T‐N+). AD was the main neuropathological diagnosis in all cases except for the A‐T+N‐ case where progressive supranuclear palsy was the main diagnosis (Figure 1). Conclusion Despite neuropathological evidence of amyloid deposition, neuronal death and neurodegeneration at autopsy, only 60% of our AD patients had a full A+T+N+ CSF profile. CSF Ab 42/40 ratio may improve correlations between biomarkers and pathology by reincorporating some of our A‐T+ patients into the A+T+ group. We are currently confirming these data by repeating the measures using modern fully‐automated assays, including CSF Ab 42/40 ratio.