Alzheimer’s Disease: New Treatment Perspectives Involving Active and Passive Immunotherapy

Neurodegenerative diseases represent nowadays one of the major health problems. Despite the efforts made to unveil the mechanism leading to neurodegeneration, it is still not entirely clear what triggers this phenomenon and what allows its progression. Nevertheless, it is accepted that neurodegeneration is a consequence of several detrimental processes, such as protein aggregation, oxidative stress, and neuroinflammation, finally resulting in the loss of neuronal functions. Starting from these evidences, there has been a wide search for novel agents able to address more than a single event at the same time, the so-called multitarget-directed ligands (MTDLs). These compounds originated from the combination of different pharmacophoric elements which endowed them with the ability to interfere with different enzymatic and/or receptor systems, or to exert neuroprotective effects by modulating proteins and metal homeostasis. MTDLs have been the focus of the latest strategies to discover a new treatment for Alzheimer’s disease (AD), which is considered the most common form of dementia characterized by neurodegeneration and cognitive dysfunctions. This review is aimed at collecting the latest and most interesting target combinations for the treatment of AD, with a detailed discussion on new agents with favorable in vitro properties and on optimized structures that have already been assessed in vivo in animal models of dementia.

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BOOK REVIEWS: Alzheimer's Disease--New Treatment Strategies (Dementia Reviews Series/1).

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.56.9.1042-b ◽

1993 ◽

Vol 56 (9) ◽

pp. 1042-1042

Author(s):

D. Bonner

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Treatment Strategies ◽

New Treatment

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Psychosis in Alzheimer’s Disease

Current Neurology and Neuroscience Reports ◽

10.1007/s11910-020-01074-y ◽

2020 ◽

Vol 20 (12) ◽

Author(s):

Clive Ballard ◽

Helen C. Kales ◽

Constantine Lyketsos ◽

Dag Aarsland ◽

Byron Creese ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Atypical Antipsychotics ◽

Cholinesterase Inhibitors ◽

Pharmacological Treatments ◽

Muscarinic Agonists ◽

Pharmacological Management ◽

Psychological Therapies ◽

New Treatment

Abstract Purpose of Review To review the incidence, treatment and genetics of psychosis in people with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Recent Findings Psychosis in Alzheimer’s disease (AD) has an incidence of ~ 10% per year. There is limited evidence regarding psychological interventions. Pharmacological management has focused on atypical antipsychotics, balancing modest benefits with evidence of long-term harms. The 5HT2A inverse agonist pimavanserin appears to confer benefit in PD psychosis with initial evidence of benefit in AD. Cholinesterase inhibitors give modest benefits in DLB psychosis. The utility of muscarinic agonists, lithium, glutamatergic and noradrenergic modulators needs further study. Summary Recent work has confirmed the importance of psychosis in MCI as well as AD. The lack of evidence regarding psychological therapies is an urgent knowledge gap, but there is encouraging evidence for emerging pharmacological treatments. Genetics will provide an opportunity for precision medicine and new treatment targets.

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Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cells ◽

10.3390/cells8090968 ◽

2019 ◽

Vol 8 (9) ◽

pp. 968 ◽

Cited By ~ 6

Author(s):

Sunitha Kodidela ◽

Kelli Gerth ◽

Sanjana Haque ◽

Yuqing Gong ◽

Saifudeen Ismael ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Extracellular Vesicles ◽

Treatment Strategies ◽

Progressive Dementia ◽

Hiv Patients ◽

Age Related ◽

Infected Cells ◽

New Treatment

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

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