Abstract
Alzheimer’s disease (AD) represents the most prevalent form of senile dementias. The disease is characterized by the occurrence of extracellular plaques, intracellular neurofibrillary tangles, a loss of neurons and synapses, hippocampus and cerebral atrophy and memory loss. Extracellular plaques consist mainly of β-amyloid peptides (Aβ), which are generated through proteolytical cleavage of the larger amyloid precursor protein (APP). Mutations in the APP gene as well as in the two presenilin genes (PSEN1/PSEN2) are responsible for the majority of familial AD (FAD) cases. All these mutations lead to an enhanced Aβ deposition, favoring mostly the generation of the longer Aβ variant containing 42 amino acids (Aβ42). In this chapter, we will briefly summarize the clinical features of AD, mild cognitive impairment being a transitional stage between the cognitive changes during normal aging and AD, as well as information on AD genetics and main pathological hallmarks. In addition, transgenic animal models, as well as current and future therapy options, will be addressed and risk factors such as diabetes will be discussed.
Similar content being viewed by others
Abbreviations
- AD:
-
Alzheimer’s disease
- ADAM:
-
A disintegrin and metalloprotease
- APH-1:
-
Anterior pharynx defective 1
- ApoE:
-
Apolipoprotein E
- APP:
-
Amyloid precursor protein
- ATP:
-
Adenosine triphosphate
- Aβ:
-
Amyloid beta
- BACE 1:
-
Beta-site APP cleaving enzyme 1
- BDNF:
-
Derived neurotrophic factor
- CA1:
-
Cornu ammonis 1
- CAA:
-
Cerebral amyloid angiopathy
- CNS:
-
Central nervous system
- CSF:
-
Cerebrospinal fluid
- CT:
-
Computer tomography
- Cu:
-
Copper
- DMII:
-
Type 2 diabetes mellitus
- DS:
-
Down syndrome
- FAD:
-
Familial Alzheimer’s disease
- FDG:
-
Fluorodeoxyglucose
- GSK-3β:
-
Glycogen synthase kinase-3β
- IDE:
-
Insulin degrading enzyme
- IGF-1:
-
Insulin-like growth factor-1
- LOAD:
-
Late-onset Alzheimer’s disease
- MAP:
-
Microtubule-associated protein
- MCI:
-
Mild cognitive impairment
- MMSE:
-
Mini mental state examination
- MRI:
-
Magnetic resonance imaging
- NFT:
-
Neurofibrillary tangles
- NMDA:
-
N-methyl-D-aspartate
- NSAID:
-
Nonsteroidal anti-inflammatory drug
- PEN-2:
-
Presenilin enhancer 2
- PET:
-
Positron emission tomography
- PHF:
-
Paired helical filaments
- PIB:
-
Pittsburgh compound B
- PSEN1:
-
Presenilin 1
- PSEN2:
-
Presenilin 2
- ROS:
-
Reactive oxygen species
- VEGF:
-
Vascular endothelial growth factor
References
Alzheimer’s Association Report (2016) 2016 Alzheimer’s disease facts and figures. Alzheimers Dement 12:459–509
Maurer K, Volk S, Gerbaldo H (1997) Auguste D and Alzheimer’s disease. Lancet 349:1546–1549
Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81:741–766
Sergeant N, Bretteville A, Hamdane M, Caillet-Boudin ML, Grognet P, Bombois S, Blum D, Delacourte A, Pasquier F, Vanmechelen E, Schraen-Maschke S, Buee L (2008) Biochemistry of Tau in Alzheimer’s disease and related neurological disorders. Expert Rev Proteomics 5:207–224
Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8:595–608
Bayer TA, Wirths O (2010) Intracellular accumulation of amyloid-beta - a predictor for synaptic dysfunction and neuron loss in Alzheimer’s disease. Front Aging Neurosci 10:2–8
De Strooper B, Vassar R, Golde T (2010) The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol 6:99–107
Nhan HS, Chiang K, Koo EH (2015) The multifaceted nature of amyloid precursor protein and its proteolytic fragments: friends and foes. Acta Neuropathol 129:1–19
Dourlen P, Kilinc D, Malmanche N, Chapuis J, Lambert JC (2019) The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? Acta Neuropathol 138:221–236
Bayer TA, Wirths O (2014) Focusing the amyloid cascade hypothesis on N-truncated Abeta peptides as drug targets against Alzheimer’s disease. Acta Neuropathol 127:787–801
Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer's disease. Lancet 368(9533):387–403
Duyckaerts C, Potier MC, Delatour B (2008) Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol 115:5–38
Wirths O, Zampar S (2020) Neuron loss in Alzheimer’s disease: translation in transgenic mouse models. Int J Mol Sci 21:8144
Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Copper C, Costafreda SG, Dias A, Fox N, Gitlin LN, Howard R, Kales HC, Kivimäki M, Larson EB, Ogunniyi A, Orgeta V, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbaek G, Teri L, Mukadam N (2020) Dementia prevention, intervention and care: 2020 report of the lancet commission. Lancet 396:413–446
Panza F, Lozupone M, Logroscino G, Imbimbo BP (2019) A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat Rev Neurol 15:73–88
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Science+Business Media, LLC, part of Springer Nature
About this entry
Cite this entry
Wirths, O., Bouter, Y., Bayer, T.A. (2021). Alzheimer’s Disease. In: Pfaff, D.W., Volkow, N.D., Rubenstein, J. (eds) Neuroscience in the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6434-1_114-4
Download citation
DOI: https://doi.org/10.1007/978-1-4614-6434-1_114-4
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-6434-1
Online ISBN: 978-1-4614-6434-1
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences
Publish with us
Chapter history
-
Latest
Alzheimer’s Disease- Published:
- 31 March 2022
DOI: https://doi.org/10.1007/978-1-4614-6434-1_114-4
-
Original
Alzheimer’s Disease- Published:
- 29 March 2016
DOI: https://doi.org/10.1007/978-1-4614-6434-1_114-3