Alzheimer's disease (AD) is increasingly prevalent worldwide, and disease-modifying treatments may soon be at hand; hence, now, more than ever, there is a need to develop techniques that allow earlier and more secure diagnosis. Current biomarker-based guidelines for AD diagnosis, which have replaced the historical symptom-based guidelines, rely heavily on neuroimaging and cerebrospinal fluid (CSF) sampling. While these have greatly improved the diagnostic accuracy of AD pathophysiology, they are less practical for application in primary care, population-based and epidemiological settings, or where resources are limited. In contrast, blood is a more accessible and cost-effective source of biomarkers in AD. In this review paper, using the recently proposed amyloid, tau and neurodegeneration [AT(N)] criteria as a framework towards a biological definition of AD, we discuss recent advances in biofluid-based biomarkers, with a particular emphasis on those with potential to be translated into blood-based biomarkers. We provide an overview of the research conducted both in CSF and in blood to draw conclusions on biomarkers that show promise. Given the evidence collated in this review, plasma neurofilament light chain (N) and phosphorylated tau (p-tau; T) show particular potential for translation into clinical practice. However, p-tau requires more comparisons to be conducted between its various epitopes before conclusions can be made as to which one most robustly differentiates AD from non-AD dementias. Plasma amyloid beta (A) would prove invaluable as an early screening modality, but it requires very precise tests and robust preanalytical protocols.

BackgroundThe identification of central nervous system (CNS) involvement by malignancies, using cytological analysis of CSF, is crucial for the appropriate treatment of patients.1 The aim of this study was to identify CSF specimen characteristics that have the highest diagnostic yield.MethodsWe conducted a retrospective review of all CSF specimens submitted for cytological analysis at Cork University Hospital from January 2010 to December 2011.Results598 CSF samples were obtained from 390 people. The difference in volume between the diagnostic categories of equivocal (29%), inadequate (17%), positive (5%) and negative (48%) was found to be statistically significant, p-value <0.05 (kruskal-wallis test). Of the 66 (17%) requiring repeat CSF sampling 25% of initial samples were inadequate, falling to 10% on second sampling. The average volume of the initial samples was 2.72 ml, increasing to 3.93 ml on repeat sampling.DiscussionConventional cytology has shown high specificity but low sensitivity, being positive in 45% to 94% of initial specimens.1 Our study shows that factors increasing the likelihood of a definite result include a sample volume greater than 3 ml, and repeating sampling.

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A 58-year-old right-handed woman presented to our institution with a 1-month history of polydipsia and polyuria. She had a remote history of neurofibroma excision by dermatology and, on examination, was noted to meet the clinical diagnostic criteria for neurofibromatosis type 1. Laboratory investigations revealed hypernatraemia and elevated serum osmolality, accompanied by reduced urinary osmolality. A subsequent water deprivation test confirmed central diabetes insipidus, which responded to treatment with desmopressin. MRI of the brain showed pituitary enlargement, which raised the possibility of an underlying pituitary adenoma or, alternatively, lymphocytic hypophysitis. Both conditions have rarely been described in neurofibromatosis.