Advances in Alzheimer's Disease: From Bench to Bedside

Abstract

In 1906, Alois Alzheimer first documented the case of Auguste Deter, a patient with a combination of cognitive deficits, psychiatric symptoms, and microscopic brain lesions. This histopathological and clinical constellation was then designated by Emil Kraepelin as Alzheimer's disease (AD) [1]. Nowadays, AD became the most common progressive neurodegenerative disease and the most common form of dementia among the elderly [2, 3]. In the clinic, the late-onset AD (LOAD) accounts for 95% of all AD cases and is currently considered as a genetic complex disorder that is probably caused by a combination of multiple risk alleles and environmental factors [4]. To date, APOE is the only unequivocally established susceptibility gene for LOAD [5]. However, it has been estimated that the variations of APOE account for less than 50% of LOAD risk, suggesting that there are additional genetic risk factors which remain to be uncovered. Recent advances in genetic approaches led to the identification of numerous risk genes for AD, which has greatly extended our knowledge on the genetic components of this disease [6]. In this special issue, the paper entitled “Clinical Genetics of Alzheimer's Disease” by Z. Zou et al. outlined these novel susceptibility genes, such as CLU, CR1, CD33, PICALM, BIN1, TREM2, and PLD3. More importantly, they summarized the recent evidence regarding the functions of these genes as well as their association with phenotypes and pathogenesis of AD. This allowed readers to get a good understanding on the research advances in the genetic basis and pathological mechanisms of this devastating disease. Regarding the neuropathology, AD is mainly characterized by the formation of extracellular neuritic plaques containing the amyloid-β peptide (Aβ) and intraneuronal accumulation of neurofibrillary tangles constituted by hyperphosphorylated tau protein. In 2002, John Hardy proposed “amyloid hypothesis,” which emphasized Aβ accumulation as the initial pathological events in the progression of AD [7]. Therefore, therapeutic strategies against Aβ, especially Aβ-induced neurotoxicity, have attracted a lot of attention in recent years.