Alzheimer's disease: Only prevention makes sense

@article{Via2018AlzheimersDO,
  title={Alzheimer's disease: Only prevention makes sense},
  author={Jos{\'e} Vi{\~n}a and Jorge Sanz-Ros},
  journal={European Journal of Clinical Investigation},
  year={2018},
  volume={48}
}
  • J. Viña, J. Sanz-Ros
  • Published 19 September 2018
  • Medicine
  • European Journal of Clinical Investigation
Alzheimer's disease therapeutics is one of the most important endeavours in today's clinical investigation. Over more than 30 years of research, no disease‐modifying treatment has been approved by either the FDA or the EMA to treat Alzheimer's disease. Recently, the evidence of pathological alterations in the brain tissue has been gathered showing that the signs of brain damage appear more than 20 years before the onset of Alzheimer's dementia. The major aim of this review is to underpin the… 
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References

SHOWING 1-10 OF 55 REFERENCES
Reversal of cognitive decline in Alzheimer's disease
TLDR
The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective and has far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype.
Epidemiology of Alzheimer disease
TLDR
An overview of the criteria used in the diagnosis of Alzheimer disease is provided, highlighting how this disease is related to, but distinct from, normal aging.
Neuropathology of Alzheimer's disease.
  • D. Perl
  • Medicine
    The Mount Sinai journal of medicine, New York
  • 2010
TLDR
It is important to recognize that distinguishing between Alzheimer's disease, especially in its early stages, and normal aging may be very difficult, particularly if one is examining the brains of patients who died at an advanced old age.
Neuropsychiatric symptoms in Alzheimer’s disease
TLDR
An Alzheimer's Association Research Roundtable was convened in the spring of 2010 to review what is known about NPS in Alzheimer's disease, to discuss classification and underlying neuropathogenesis and vulnerabilities, and to formulate recommendations for new approaches to tailored therapeutics.
Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers
TLDR
It is speculated that the two major proteinopathies underlying AD biomarker changes, amyloid β (Aβ) and tau, might be initiated independently in sporadic AD, in which it is hypothesised that an incident Aβ pathophysiology can accelerate antecedent limbic and brainstem tauopathy.
The case for rejecting the amyloid cascade hypothesis
  • K. Herrup
  • Psychology, Medicine
    Nature Neuroscience
  • 2015
TLDR
The proposition that the authors are over-reliant on amyloid to define and diagnose AD is explored and that the time has come to face their fears and reject the amyloids cascade hypothesis.
A phase 3 trial of semagacestat for treatment of Alzheimer's disease.
TLDR
As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability, and semagACestat was associated with more adverse events, including skin cancers and infections.
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
TLDR
In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner, accompanied by a slowing of clinical decline measured by Clinical Dementia Rating—Sum of Boxes and Mini Mental State Examination scores.
Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
TLDR
Aβ immunization reduces both deposition of cerebral fibrillar Aβ and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of Aβ in the brain, which implies that either a ∼50% reduction in dense-cored Aβ plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic Aβ species.
Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models
The goal of this review is to discuss how behavioral tests in mice relate to the pathological and neuropsychological features seen in human Alzheimer's disease (AD), and present a comprehensive
...
1
2
3
4
5
...