Neurotoxicity Research

, Volume 22, Issue 3, pp 182–194 | Cite as

Alzheimer’s Disease Pathologic Cascades: Who Comes First, What Drives What



This review discusses known and speculated relationships between Alzheimer’s disease (AD) biochemical, molecular, and histologic phenomena. In the AD brain, various pathologies including neuritic plaques, neurofibrillary tangles, synaptic loss, oxidative stress, cell cycle re-entry, and mitochondrial changes have all been described. In an attempt to explain what exactly goes wrong in the AD brain various investigators have proposed different heuristic and hierarchical schemes. It is important to accurately define the AD pathology hierarchy because treatments targeting the true apex of its pathologic cascade arguably have the best chance of preventing, mitigating, or even curing this disease.


Aging Alzheimer’s disease Amyloid Brain Oxidative stress Mitochondria 


Beta amyloid


Alzheimer’s disease


Amyloid precursor protein


Beta secretase


Cytochrome oxidase


Electron transport chain


Familial British dementia


Familial Danish dementia


Genome wide association study


Hereditary cerebral hemorrhage with amyloidosis


Mitochondrial DNA


Nitric oxide synthase


Reactive nitrogen species


Reactive oxygen species


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Kansas Medical CenterKansas CityUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Kansas Medical CenterKansas CityUSA
  3. 3.Department of Molecular and Integrative PhysiologyUniversity of Kansas Medical CenterKansas CityUSA
  4. 4.University of Kansas School of MedicineKansas CityUSA

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