Correspondence

Age, Neuropathology, and Dementia

N Engl J Med 2009; 361:1118September 10, 2009

Article

To the Editor:

Savva et al. (May 28 issue)1 reported on the assessment of the pathologic features of 456 brains donated from older old persons with or without dementia. Although their results challenge the current idea that neuritic plaques and tangles are a hallmark of Alzheimer's disease in a younger old cohort, the results should still merit reexamining the detailed mechanisms of how these pathologic factors induce neuronal loss or dementia. Furthermore, it is essential to incorporate neuronal and synaptic loss into a quantitative evaluation of pathologic changes in both younger and older cohorts of persons with dementia; pathologic changes evidently occurred in the cerebral cortex of patients with Alzheimer's disease2 and might result in the consistent brain atrophy seen in patients of increasing age in this study. In addition to age, mixed pathologic factors such as proteins associated with dysfunction, trophic factors (e.g., brain-derived neurotrophic factor released in situ), and their interaction with neuronal and synaptic plasticity3-5 should be also taken into account when assessing the effects of intervention in patients with dementia.

Liang-Wei Chen, Ph.D.
Fourth Military Medical University, Xi'an, China
lwchen@fmmu.edu.cn

5 References

1. 1

   Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C. Age, neuropathology, and dementia. N Engl J Med 2009;360:2302-2309
   Full Text | Web of Science | Medline

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   Wasling P, Daborg J, Riebe I, et al. Synaptic retrogenesis and amyloid-beta in Alzheimer's disease. J Alzheimers Dis 2009;16:1-14
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   Adalbert R, Nogradi A, Babetto E, et al. Severely dystrophic axons at amyloid plaques remain continuous and connected to viable cell bodies. Brain 2009;132:402-416
   CrossRef | Web of Science | Medline

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   Nagahara AH, Merrill DA, Coppola G, et al. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat Med 2009;15:331-337
   CrossRef | Web of Science | Medline

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   Lauren J, Gimbel DA, Nygaard HB, et al. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 2009;457:1128-1132
   CrossRef | Web of Science | Medline