Therapy for Alzheimer’s disease: Missing targets and functional markers?

Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives

“…More specifically (Table 1), Aβ(3-10) [70][71][72] and Aβ(1-6) were among the peptide epitopes used [73]; different copy numbers of the latter were used in another attempt to develop new Aβ-vaccines [74]. In addition, Aβ(1-6) and Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were used for the synthesis of 4-branched multiple-antigen peptides (MAP) 4 and subsequently administered to mice to develop Aβ specific antibodies [75]. Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) was also used in a cholera toxin B subunit/silkworm pupa vaccine [76] as well as in a yeast-based vaccine (Y-5A15) [77].…”

“…In addition, Aβ(1-6) and Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were used for the synthesis of 4-branched multiple-antigen peptides (MAP) 4 and subsequently administered to mice to develop Aβ specific antibodies [75]. Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) was also used in a cholera toxin B subunit/silkworm pupa vaccine [76] as well as in a yeast-based vaccine (Y-5A15) [77]. Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) was used in a combination vaccine (AV-1959R/AV-1980R) targeting both Aβ and tau [78].…”

“…AD appears in two forms: sporadic AD, which is late-onset, i.e., symptoms begin after the age of 65, and represents the vast majority of AD cases (~95%), and familial AD, an early-onset and dominantly inherited disease, which accounts for a low percentage (~5%) of AD cases [5]. Although age is the major risk factor for sporadic AD, the presence of ApoE-ε4 genetic polymorphism highly increases the possibilities of developing the disease in persons older than 65 years [8]. Moreover, a large genome meta-analysis of clinically diagnosed late-onset AD cases confirmed 20 previously reported risk loci and also identified some new ones [5], associated e.g., with lipid metabolism and immunity [3].…”

“…Moreover, a large genome meta-analysis of clinically diagnosed late-onset AD cases confirmed 20 previously reported risk loci and also identified some new ones [5], associated e.g., with lipid metabolism and immunity [3]. On the other hand, familial AD affects younger individuals and is associated with mutated forms of the amyloid precursor protein (APP) and the core proteins of γ-secretase complex, presenilin 1 and presenilin 2 (PS1 and PS2), the presence/function of which result in accumulation of amyloid β peptide (Aβ) and formation of extracellular amyloid plaques [8,9]. In general, according to the well-known "amyloid cascade hypothesis" [10], under certain circumstances neurotoxic Aβ can be produced, accumulated/aggregated, and ultimately damage neurons, thus leading to dementia [3].…”

“…Thus, a few drugs for AD have been approved by the US Food and Drug Administration (FDA), including donepezil, rivastigmine, and galantamine (cholinesterase inhibitors), memantine (an N-methyl-D-aspartate receptor partial antagonist), and a combination of donepezil and memantine. All these drugs, however, have limited effectiveness and they do not reverse the progression of the disease or improve cognitive dysfunction, but they rather delay the deterioration of AD symptoms for a limited time period [8]. Recently, a fully human monoclonal antibody targeting Aβ, aducanumab, has been approved by the FDA, although there has been some controversy concerning the overall efficacy of this passive immunotherapeutic agent [20][21][22][23][24].…”