CSF Alzheimer’s biomarkers in clinical practice

Abstract

AbstractBackgroundCSF biomarkers are well validated and a useful tool for the diagnosis of Alzheimer’s disease (AD). However, in some cases results are not consistent. In this study we examine to which extent CSF biomarkers support diagnosis in clinical practice.MethodAnalysis of 141 consecutive CSF samples of patients referred to our memory clinic with suspected cognitive decline, using the Lumipulse G600II chemiluminescent immunoassay (Fujirebio, Spain) to determine Ab‐42/Ab‐40 ratio (A+ if <0.068), total Tau (N+ if >410 pg/ml), and phospho‐Tau (T+ if >59 pg/ml).Clinical diagnosis was classified into three categories: AD, degenerative non‐AD, and non degenerative, considering current clinical criteria at last visit.Based on biomarkers, we separated the groups as follows: negative for AD (A‐T‐N‐ and A‐T‐N+), positive for AD (A+T+N+ and A+T+N‐), cases with amyloidosis A+ but T‐ (A+T‐N+; A+T‐N‐), and cases without amyloidosis A‐ but T+ (A‐T+N+).Result50,5% of the patients had a positive AD result that correlated in a majority of cases with a clinical amnestic AD phenotype or other highly related phenotypes (logopenic aphasia and posterior cortical atrophy). The exceptions were 5 cases meeting diagnostic criteria for non‐fluent/agrammatic aphasia or corticobasal syndrome.37% had a negative AD result which correlated with a clinical diagnosis of non‐AD neurodegeneration (25 cases) or non degenerative (27 cases).Therefore, in 87% of the cases CSF biomarkers supported a clinical diagnosis.On the other hand, 18 cases (13%) had some inconsistencies within biomarkers: 7 with A‐ and 11 with A+ results. As regards clinical diagnosis, all A‐T+N+ and many of the patients with A+ biomarkers (8/11) had been considered AD phenotypes. In two of the cases with A+T‐N‐, an AD diagnosis was later confirmed, respectively, by a positive PET‐amyloid study and full positive CSF biomarkers analyzed two years later.No differences were found in family history, age of onset, or age at lumbar puncture between the groups of AD positive biomarkers and just amyloidosis A+.ConclusionCSF biomarkers were clearly supportive of the clinical diagnosis in a majority of the cases of our cohort. However, in 13% of the cases, most of them with an AD type phenotype, biomarkers were unclear.