Alzheimer's disease (AD) is a multifactorial and heterogeneous disease in both its clinical and histopathological appearance. In more than 99% of cases the cause of the disease is not understood. Independent of its cause, AD is clinically characterised by a developing dementia and histopathologically characterised by neuronal degeneration.Although the presence of neurofibrillary tangles (NFTs) and neurotic The development of biomarkers for AD is challenging as it is complicated by several factors. In addition to the variability in clinical features and multiple molecular aetiologies, the development of AD biomarkers is burdened with a diagnostic imprecision as confirmation of the disease preferentially has to await a post mortem histopathological examination.The long asymptomatic prodromal stages, rates of progression and complex disease genetics complicate the situation further. In this article we will review the current developments in the field of biomarkers for the detection of AD in blood.
Single-component BiomarkersThe physiology of the blood-brain barrier limits potential biomarkers that are closely associated to brain pathophysiology to small molecules, lipophilic molecules and molecules with specific transporters. 12 Brainderived proteins and metabolites that pass into the plasma will also become markedly diluted in a biochemically complex medium. 12 Moreover, it is not known whether there are any direct pathophysiological processes associated with AD in blood cells. The traditional approach of using one or a few closely related molecules as a biomarker, a single-component biomarker, in plasma, serum or blood has been utilised since the late 1990s. [13][14][15] However, their usefulness has been limited, mainly due to discrepant results between studies.
Amyloid β-proteinAβ can be detected in plasma and is thus a compelling candidate biomarker for AD. The plasma total Aβ or Aβ42 was increased in familial AD with presenilin or APP mutations 16,17 and in Down's syndrome with APP triplication, 18 which raises the possibility that sporadic AD may also be associated with detectable and diagnostic changes in Aβ plasma levels. Animal models suggest that Aβ can pass between cerebrospinal fluid (CSF) and plasma compartments, 19,20 but this has yet to be confirmed in humans. APP is also produced by platelets and is, therefore, an alternative source for the APP and Aβ pools found in plasma.