Parkinson’s disease (PD) and Alzheimer’s disease (AD) are two of the most common incurable neurological disorders affecting the worldwide population over 60 years of age and are characterized by the progressive loss of either motor or cognitive functions in affected individuals. Therefore, a critical review of the disease-modifying therapy pipeline for Alzheimer’s disease is needed. Small molecules, mAbs, or multimodal strategies showing promise in animal studies have not confirmed that promise in the clinic (where small to moderate changes in clinical efficacy have been observed), and therefore, there is a significant unmet need for a better understanding of the AD pathogenesis and the exploration of alternative etiologies and therapeutic effective disease-modifying therapies strategies for AD. Recently, Aducanumab, the first disease-modifying therapy (DMT) has been approved for AD, and several DMTs are in advanced stages of clinical development or regulatory review. Improvements to the approved therapies, such as easier routes of administration and reduced dosing frequencies, along with the developments of new strategies and combined treatments are expected to occur within the next decade and will positively impact the way the disease is managed.

The current competitive landscape in AD consists of symptomatic treatments, of which there are currently six approved medications: three AChEIs (donepezil, rivastigmine, and galantamine), one NMDA-R antagonist (memantine), one combination therapy (memantine/donepezil), and GV-971 (sodium oligomannate, a mixture of oligosaccharides derived from algae) only approved in China. Pathologically, AD is characterized by the deposition of amyloid β-peptide (Aβ) in the neuropil (neuritic plaques) and blood vessels (amyloid angiopathy), and by the accumulation of hyperphosphorylated tau in neurons (neurofibrillary tangles) in the brain, with associated loss of synapses and neurons, together with glial activation, and neuroinflammation, resulting in cognitive deficits and eventually dementia. Worldwide, approximately 50 million people are living with dementia, with AD comprising 60–70% of cases. Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative brain disorder and the most common form of dementia in the elderly with a long presymptomatic phase. Alois Alzheimer first described in a patient “a peculiar severe disease process of the cerebral cortex”, people suffering from this pathology have been waiting for a breakthrough therapy.

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