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Review
. 2024 Dec 16:18:e2024VR01.
doi: 10.1590/1980-5764-DN-2024-VR01. eCollection 2024.

Physiopathological mechanisms underlying Alzheimer's disease: a narrative review

Eliasz Engelhardt  1 , Elisa de Paula França Resende  2   3 , Karina Braga Gomes  4
Affiliations
Review

Physiopathological mechanisms underlying Alzheimer's disease: a narrative review

Eliasz Engelhardt et al. Dement Neuropsychol. .

Abstract
in English, Portuguese

The neuropathological signature of Alzheimer's disease (AD) comprises mainly amyloid plaques, and neurofibrillary tangles, resulting in synaptic and neuronal loss. These pathological structures stem from amyloid dysfunctional metabolism according to the amyloid cascade hypothesis, leading to the formation of plaques, and apparently inducing the initiation of the abnormal tau pathway, with phosphorylation and aggregation of these proteins, ultimately causing the formation of tangles. In this narrative review, the existing hypothesis related to the pathophysiology of AD were compiled, and biological pathways were highlighted in order to identify the molecules that could represent biological markers of the disease, necessary to establish early diagnosis, as well as the selection of patients for therapeutical interventional strategies.

A assinatura neuropatológica da doença de Alzheimer (DA) compreende principalmente placas amiloides e emaranhados neurofibrilares, resultando em perda sináptica e neuronal. Essas estruturas patológicas decorrem de um metabolismo amiloide disfuncional, conforme a hipótese da cascata amiloide, levando à formação de placas e aparentemente induzindo o início da via anormal do metabolismo da proteína tau, com fosforilação e agregação dessas proteínas, culminando na formação dos emaranhados. Nesta revisão narrativa, as hipóteses existentes relacionadas à fisiopatologia da DA foram compiladas, e as vias biológicas foram destacadas para identificar as moléculas que poderiam representar marcadores biológicos da doença, necessários para estabelecer o diagnóstico precoce, bem como a seleção de pacientes para estratégias de intervenção terapêutica.

Keywords: Alzheimer Disease; Amyloid; Amyloid Plaque; Biomarkers; Neurofibrillary Tangles; Tau Proteins.

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Conflict of interest statement

Disclosure: EPFR received support from Proneuro for the preparation of educational materials, from Novo Nordisk for conference attendance, and from Roche for participation in educational activities. EE and KBG have no conflict of interest to declare.

Figures

Figure 1
Figure 1. Amyloid Precursor Proteins isoforms, with three different lengths.
Figure 2
Figure 2. Amyloid precursor protein cleavage of non-amyloidogenic and amyloidogenic pathways.
Figure 3
Figure 3. The six tau protein isoforms with four and three repeats.
Figure 4
Figure 4. Tau pathways. A. Neuron with microtubules (blue). [a] Normal state – healthy neuron – arrow pointing to normal microtubule bounded by tau proteins. [b] Pathological state - impaired neuron – arrow pointing to disrupted microtubule due to presence of p-tau proteins. B. aggregation process of p-tau monomers and formation of paired helical filament (and next neurofibrillary tangles).
See this image and copyright information in PMC

References

    1. Bayer TA, Wirths O, Majtényi K, Hartmann T, Multhaup G, Beyreuther K, et al. Key factors in Alzheimer’s disease: β-amyloid precursor protein processing, metabolism and intraneuronal transport. Brain Pathol. 2001;11(1):1–11. doi: 10.1111/j.1750-3639.2001.tb00376.x. - DOI - PMC - PubMed
    1. DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener. 2019;14(1):32. doi: 10.1186/s13024-019-0333-5. - DOI - PMC - PubMed
    1. Duyckaerts C, Delatour B, Potier MC. Classification and basic pathology of Alzheimer disease. Acta Neuropathol. 2009;118(1):5–36. doi: 10.1007/s00401-009-0532-1. - DOI - PubMed
    1. Thal DR, Rüb U, Orantes M, Braak H. Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology. 2002;58(12):1791–1800. doi: 10.1212/wnl.58.12.1791. - DOI - PubMed
    1. Alzheimer A. Über eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift fur Psychiatrie und phychish-Gerichtliche Medizin. 1907;64:146–148.

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