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Synapse loss in Alzheimer’s disease

Synapse loss is the hallmark of Alzheimer’s disease that correlates best with impaired memory, and is thought to occur even before the onset of clinical symptoms.

Pathological hallmarks of Alzheimer’s disease

Alzheimer’s disease is characterised by beta-amyloid plaques, neurofibrillary tangles, neurone loss and synapse loss [1-4]. Compared with the other hallmarks of Alzheimer’s disease, synapse loss correlates best with impaired memory, and is believed to occur early in the disease process, even before the onset of clinical Alzheimer’s disease symptoms [2-4].

Synapse loss and memory

While synapse loss occurs during normal aging, it is far more pronounced in Alzheimer’s disease [1-3,5]. The cognitive changes that occur in Alzheimer’s disease patients are related to the loss of functional connections in the brain associated with synapse loss [1]. A correlation has been observed between the number of synapses and memory, with memory performance declining as the number of synapses decreases [3]. A specific combination of nutrients is required for the formation of new synapses [6-16].

  • Alzheimer’s disease is characterised by beta amyloid plaques, neurofibrillary tangles and loss of synapses [4]

    Alzheimer’s disease is characterised by beta amyloid plaques, neurofibrillary tangles and loss of synapses [4]

    Synapse loss occurs early in the disease process, even before the onset of the clinical symptoms of Alzheimer’s disease [2-4].

  • Reduced number of synapses in MCI and Alzheimer’s disease compared with control subjects [3]

    Reduced number of synapses in MCI and Alzheimer’s disease compared with control subjects [3]

    Synapse loss appears to be directly correlated with the progressive cognitive decline observed in Alzheimer’s disease [3].

  • Correlation between number of synapses and memory performance [3]

    Correlation between number of synapses and memory performance [3]

    As the number of synapses decrease, memory performance declines [3].

References

  1. Terry RD, et al. Physical basis of cognitive alterations in Alzheimer’s disease: Synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991;30:572-580. 
  2. Terry RD. Alzheimer’s disease and the aging brain. J Geriatr Psychiatry Neurol 2006;19:125-128. 
  3. Scheff SW, et al. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging 2006;27:1372-1384.
  4. Sperling RA, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:280-292.
  5. Terry RD and Katzman R. Life span and synapses: will there be a primary senile dementia? Neurobiol Aging. 2001;22:347-348.
  6. Wurtman RJ, et al. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006;1088:83-92.
  7. Cansev M, et al. Restorative effects of uridine plus docosahexaenoic acid in a rat model of Parkinson's disease. Neurosci Res. 2008;62:206-209.
  8. Sakamoto T, et al. Oral supplementation with docosahexaenoic acid and uridine-5'-monophosphate increases dendritic spine density in adult gerbil hippocampus. Brain Res. 2007;1182:50-59.
  9. Holguin S, et al. Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats. Behav Brain Res. 2008;191:11-16.
  10. Holguin S, et al. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. FASEB J. 2008;22:3938-3946. 
  11. Cansev M, et al.  Giving uridine and/or docosahexaenoic acid orally to rat dams during gestation and nursing increases synaptic elements in brains of weanling pups. Dev Neurosci. 2009;31:181-192.
  12. Cansev M and Wurtman RJ. Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils. Neuroscience. 2007;148:421-431.
  13. Wang L, et al. Dietary supplementation with uridine-5'-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat. Brain Res. 2007;1133:42-48.
  14. Richardson UI, et al. Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells. Brain Res. 2003;971:161-167. 
  15. Richardson UI and Wurtman RJ. Polyunsaturated fatty acids stimulate phosphatidylcholine synthesis in PC12 cells. Biochim Biophys Acta. 2007;1771:558-563. 
  16. van Wijk N, et al. Plasma choline concentration varies with different dietary levels of vitamins B6, B12 and folic acid in rats maintained on choline-adequate diets. Br J Nutr. 2012;107:1408-1412.