Pathogenesis of Alzheimer's disease - PubMed (original) (raw)

Review

Pathogenesis of Alzheimer's disease

Russell H Swerdlow. Clin Interv Aging. 2007.

Abstract

Alzheimer's disease (AD) is incredibly common. Increasing longevity ensures its prevalence will rise even further. Ongoing efforts to understand AD pathogenesis reveal numerous tantalizing leads. Formulating a comprehensive AD pathogenesis theory capable of incorporating these disparate leads, though, has proven difficult. This review discusses current attempts to formulate a comprehensive AD pathogenesis theory. In doing so, it focuses on clinical and molecular relationships between AD and aging. A better understanding of these relationships could inform and impact future development of AD-directed treatment strategies.

PubMed Disclaimer

Figures

Figure 1

Figure 1

The amyloid cascade hypothesis. A black box is shown in the middle of the figure, since mechanisms through which Aβ42 drives downstream pathology are not well defined.

Figure 2

Figure 2

Alzheimer’s disease dementia develops over decades. Those with more cognitive reserve and slower decline trajectories dement at the oldest ages. Those with less cognitive reserve and more rapid decline trajectories dement at younger ages.

Figure 3

Figure 3

Cytochrome oxidase activity may influence cognitive decline rates. Cytochrome oxidase activity was assayed in cybrid lines expressing mtDNA from 15 different AD subjects. The youngest AD mtDNA donors tended towards lower activies. Nine cybrid lines expressing mtDNA from control subjects indicate at most subtle age-related activity reductions.

Figure 4

Figure 4

The mitochondrial cascade hypothesis.

References

    1. Alzheimer A. Uber eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiat Psych-Gerichtl Med. 1907;64:146–8.
    1. Amaducci LA, Rocca WA, Schoenberg BS. Origin of the distinction between Alzheimer’s disease and senile dementia: How history can clarify nosology. Neurology. 1986;36:1497–9. - PubMed
    1. Anandtheerthavarada HK, Biswas G, Robin MA, Avadhani MG. Mitochondrial targeting and a novel transmembrane arrest of Alzheimer’s precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol. 2003;16:41–54. - PMC - PubMed
    1. Arendt T. Alzheimer’s disease as a loss of differentiation control in a subset of neurons that retain immature features in the adult brain. Neurobiol Aging. 2000;21:783–96. - PubMed
    1. Blacker D, Tanzi RE. The genetics of Alzheimer disease: Current status and future prospects. Arch Neurol. 1998;55:294–6. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources