Cerebrospinal Fluid Biomarkers in Clinical Subtypes of Early-Onset Alzheimer's Disease

Abstract

Background/Aims: Accurate diagnosis of sporadic early-onset Alzheimer's disease (EOAD) can be challenging, and cerebrospinal fluid (CSF) biomarkers may assist in this process. We compared CSF indices between three EOAD subtypes: amnestic, logopenic progressive aphasia (LPA), and posterior cortical atrophy (PCA). Methods: We identified 21 amnestic EOAD, 20 LPA, and 12 PCA patients with CSF data, which included amyloid β_1-42 (Aβ42), total tau (t-tau), phospho-tau₁₈₁ (p-tau), and Aβ42/t-tau index (ATI) levels. Results: Aβ42 and ATI levels were similar across groups, but t-tau and p-tau levels were significantly lower in PCA patients. Conclusions: The Aβ42 and ATI data confirm the commonality of the Aβ pathology in EOAD. The lower tau indices in PCA patients may reflect differences in the distribution of neurofibrillary tangles or rates of neurodegeneration.

Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants of probable Alzheimer's disease

“…In line with previous studies (Baumann, et al, 2010, Bouwman, et al, 2009, Coppi, et al, 2014, de Souza, et al, 2011a, de Souza, et al, 2011b, Magnin, et al, 2014, Santangelo, et al, 2014, Seguin, et al, 2011, Teng, et al, 2014), we found that CSF Aβ 42 concentrations were similar across clinical variants of probable AD, although we narrowed the dynamic range by including only patients within the pathological range for Aβ. Discrepant findings for t-tau and p-tau in probable AD variants have been reported previously (Baumann, et al, 2010, Bouwman, et al, 2009, Coppi, et al, 2014, de Souza, et al, 2011a, de Souza, et al, 2011b, Magnin, et al, 2014, Santangelo, et al, 2014, Seguin, et al, 2011, Teng, et al, 2014), but in this relatively large study we observed comparable CSF levels in all probable AD variants and the prevalence of abnormal t-tau and p-tau concentrations was essentially the same across AD phenotypes.…”

“…Discrepant findings for t-tau and p-tau in probable AD variants have been reported previously (Baumann, et al, 2010, Bouwman, et al, 2009, Coppi, et al, 2014, de Souza, et al, 2011a, de Souza, et al, 2011b, Magnin, et al, 2014, Santangelo, et al, 2014, Seguin, et al, 2011, Teng, et al, 2014), but in this relatively large study we observed comparable CSF levels in all probable AD variants and the prevalence of abnormal t-tau and p-tau concentrations was essentially the same across AD phenotypes. This is an important finding as CSF biomarkers have been incorporated in research criteria for AD and are increasingly used in clinical practice (Duits, et al, 2014, Mattsson, et al, 2012).…”

“…Second, we did not examine diagnostic sensitivity for CSF Aβ 42 concentrations or tau/Aβ 42 ratios, since we excluded patients with negative Aβ 42 markers to reduce the possibility of clinical misdiagnosis in EOAD and LOAD (Ossenkoppele, et al, 2013, Sanchez-Juan, et al, 2014) and to rule out the small proportion of PCA and lvPPA clinical syndromes that are caused by non-Aβ pathologies (Crutch, et al, 2012). This approach seems justified, as previous studies did not detect differences in CSF Aβ 42 between AD variants (Baumann, et al, 2010, Bouwman, et al, 2009, Coppi, et al, 2014, de Souza, et al, 2011a, de Souza, et al, 2011b, Magnin, et al, 2014, Santangelo, et al, 2014, Seguin, et al, 2011, Teng, et al, 2014), so we could focus on the less established diagnostic performance of t-tau and p-tau. Third, we used three different MRI scanner types.…”

“…Previous studies on CSF biomarkers in distinct clinical variants of probable AD have shown that CSF Aβ 42 levels are reduced (reflecting greater amyloid burden) independent of phenotype (Baumann, et al, 2010, Bouwman, et al, 2009, Coppi, et al, 2014, de Souza, et al, 2011a, de Souza, et al, 2011b, Magnin, et al, 2014, Santangelo, et al, 2014, Seguin, et al, 2011, Teng, et al, 2014). In contrast, for CSF t-tau and p-tau results have shown discrepancies between studies.…”

“…Some studies have found comparable t-tau and p-tau levels between amnestic AD and PCA (Baumann, et al, 2010, Coppi, et al, 2014, de Souza, et al, 2011a, de Souza, et al, 2011b, Seguin, et al, 2011), amnestic AD and lvPPA (Santangelo, et al, 2014, Teng, et al, 2014), and between EOAD and LOAD (Bouwman, et al, 2009). One study found lower CSF t-tau and p-tau levels in PCA than in lvPPA and amnestic AD (Teng, et al, 2014) and another study found higher CSF t-tau and p-tau levels in lvPPA compared to amnestic AD (Magnin, et al, 2014). In general, sample sizes of these studies have been small, included only two or three different clinical variants of probable AD and did not always select for patients with abnormal CSF biomarker profiles.…”