Molecular mechanisms for Alzheimer's disease: implications for neuroimaging and therapeutics

J Neurochem. 2006 Jun;97(6):1700-25. doi: 10.1111/j.1471-4159.2006.03989.x.


Alzheimer's disease is a progressive neurodegenerative disorder characterised by the gradual onset of dementia. The pathological hallmarks of the disease are beta-amyloid (Abeta) plaques, neurofibrillary tangles, synaptic loss and reactive gliosis. The current therapeutic effort is directed towards developing drugs that reduce Abeta burden or toxicity by inhibiting secretase cleavage, Abeta aggregation, Abeta toxicity, Abeta metal interactions or by promoting Abeta clearance. A number of clinical trials are currently in progress based on these different therapeutic strategies and they should indicate which, if any, of these approaches will be efficacious. Current diagnosis of Alzheimer's disease is made by clinical, neuropsychologic and neuroimaging assessments. Routine structural neuroimaging evaluation with computed tomography and magnetic resonance imaging is based on non-specific features such as atrophy, a late feature in the progression of the disease, hence the crucial importance of developing new approaches for early and specific recognition at the prodromal stages of Alzheimer's disease. Functional neuroimaging techniques such as functional magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography and single photon emission computed tomography, possibly in conjunction with other related Abeta biomarkers in plasma and CSF, could prove to be valuable in the differential diagnosis of Alzheimer's disease, as well as in assessing prognosis. With the advent of new therapeutic strategies there is increasing interest in the development of magnetic resonance imaging contrast agents and positron emission tomography and single photon emission computed tomography radioligands that will permit the assessment of Abeta burden in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / therapy
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Diagnostic Imaging*
  • Humans
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology


  • Amyloid beta-Peptides