Over 55 million people worldwide live with dementia, the main cause of dependency among the elderly. Alzheimer’s disease accounts for over 60% of dementia cases. The healthcare costs are staggering: US$ 1.3 trillion yearly cost of dementia, half of which is represented by informal care.
Yet, it is estimated that up to 75% of people suffering from dementia do not receive a diagnosis, hence no adequate treatment or specialised care. Alzheimer's disease (AD), like other neurodegenerative diseases, is very expensive to diagnose. People over 65 require a CT or an MRI. From Quebec, Canada, to Bucharest, Romania, the price of getting a CT investigation is in the region of EUR 200, not including the cost of doctors’ visits (family practitioner, neurologist) and blood work. The cost of an MRI investigation is more than double. In countries such as Romania, there is the option to wait several months for free imaging investigations, but this is complicated and difficult to obtain because there is no national dementia plan, therefore funds may run out very quickly as national healthcare plans are prioritised. This situation is far from unique: 75% of WHO member states do not have a national dementia plan, which means funds are not specifically allocated to provide free access to diagnosis and treatment plans.
Needless to say, a cure for AD is desperately needed. A lot of research has been done in the past few years, with mixed results. For example, during 2021 there were 152 trials assessing new therapies for AD: 28 treatments in Phase 3 trials, 74 in Phase 2, and 24 in Phase 1. The majority of drugs in trials (82.5%) targeted the underlying biology of AD with the intent of disease modification; 10.3% were putative cognitive enhancing agents; and 7.1% were drugs being developed to reduce neuropsychiatric symptoms (Cummings, J. et al, 2021). The majority of drugs targeting the underlying biology of AD were aimed at the amyloid-β (Aβ) pathway. Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of AD pathophysiology (Hampel, H. et al, 2021). While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under investigation, the established biochemical alterations of the Aβ cycle are a core biological hallmark of AD. However, the results following patient use were not as promisiong as it was hoped.
Further evidence suggests that Aβ plays a role in triggering an imbalance in cellular signaling that leads to tau hyperphosphorylation. Thus tau became a target of disease modification therapies as well. Tau is a microtubule-associated protein, the main component of the intracellular filamentous inclusions that are involved in neurodegenerative diseases known as tauopathies, including Alzheimer disease (AD) (Gao Y. et al, 2018). In healthy brains, tau contributes to preserving the structural integrity of the neuron's axon, ensuring the proper transport of essential nutrients and signals throughout the cell. In affected brains, hyperphosphorylated or abnormally-phosphorylated tau proteins detach from their microtubules (which make possible the axonal transport), misfold and clump together in intraneuronal neurofibrillary tau tangles, which are stable constructs, difficult to break. Tau tangles are toxic and lead to cell inflammation and eventual cell death (Kaštelan et al., 2023).
