Neurology Central

Alzheimer’s disease lymphocytes: potential for biomarkers?


The neurodegenerative disease described by Alois Alzheimer in 1906 is now recognized as a major aging-related dementia worldwide, affecting more than 35 million individuals. With the demographic shift toward aging societies, this number is expected to double every 20 years, to an estimated 135.5 million worldwide afflicted with the disease by 2050 [1]. The global costs related to diminished social functioning in AD patients are similar to the financial burdens of heart disease and cancer, placing Alzheimer’s disease (AD) among major public health concerns [2].

AD develops for tens of years in the preclinical phase before the onset of clinical symptoms, such as cognitive, memory and behavioral impairments associated with the progressive and irreversible loss of brain neurons [3]. Mounting evidence indicates that the effectiveness of therapeutic modalities critically depends on early diagnosis of AD, before massive neuron loss. In 2013, this conclusion was highlighted by the US FDA guidelines for new AD drugs. However, despite intense research worldwide, no diagnostic methods are currently available for preclinical AD, and existing AD treatments are only symptomatic. This reflects the fact that the cause(s) of AD and its molecular pathomechanism are far from being understood. The main concept, known as the amyloid cascade hypothesis, refers to Aβ deposits in the AD brain [4,5]. This hypothesis has been put at center-stage by the identification of rare familial AD cases linked to mutations in one of the three genes encoding proteins involved in the amyloidogenic production of Aβ: APP and presenilins [6]. Thus, it is suggested that Aβ is the primary and main cause of the disease, and Aβ aggregation initiates a cascade of pathological events characteristic for AD, such as hyperphosphorylation of neuronal tau protein, microglial activation and finally synapse and cell loss [4–6]. However, mounting evidence indicates that in sporadic AD Aβ aggregation is preceded by earlier molecular changes, and that only the final step of the sporadic AD and familial AD pathogeneses are common and dominated by the overproduction of Aβ.

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