Systemic inflammation and disease progression in Alzheimer disease
Angela R.Kamer, NYU College of Dentistry, Dept of Periodontics and Implant Dentistry
Published December 12, 2009
We read the article by Holmes et al. with great interest. [1] Holmes continues his pioneering work [2] and he and his co-authors now address a significant and highly controversial question: Does peripheral inflammation contribute to the progression of Alzheimer disease (AD)? Plasma/serum markers of systemic inflammation such as CRP or proinflammatory cytokines in predicting cognitive decline have been studied. However, Holmes et al. assessed the added effect of acute peripheral inflammatory events to the systemic TNF-alpha on the cognitive decline.
We examined 18 AD patients and 16 cognitively normal subjects (NL) and found that the number of positive IgG antibody tests against periodontopathic bacteria and TNF-alpha level independently associated with clinical AD. [3] The number of positive IgG antibodies to periodontopathic bacteria significantly improved the TNF-alpha classification of clinical AD and NL subjects. These results support Holmes et al.’s findings and suggest that when investigating the role of peripheral inflammation in the progression of AD or cognitive decline, evaluating just plasma/serum proinflammatory markers may not be sufficient. Acute and chronic inflammatory events are highly complex processes and may not be reflected in the value of one specific cytokine.
It is also possible that plasma/serum proinflammatory markers add additional value to the acute/chronic inflammatory events in predicting cognitive decline in NL or AD. Proinflammatory markers such as TNF-alpha represent the ongoing or past inflammatory events and the nature of the host response, whether normal or disregulated. [4]
When evaluating the effect of peripheral inflammations on cognitive decline or AD progression, it is important to combine the inflammatory events with measures of inflammatory response.
References
1. Holmes C, Cunningham C, Zotova E, et al. Systemic inflammation and disease progression in Alzheimer disease. Neurology 2009;73:768-774.
2. Holmes C, El-Okl M, Williams AL, Cunningham C, Wilcockson D, Perry VH. Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease. J Neurol Neurosurg Psychiatry 2003;74:788-789.
3. Kamer AR, Craig RG, Pirraglia E, et al. TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects. J Neuroimmunol. Epub 2009 Sep 19.
4. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol 2009;39:687-699.
Disclosure: Dr. Kamer served as Associate Editor for Journal of Alzheimer’s disease; receives funds from NIH [AG036502-01 (Coinvestigator), NIH/NCRR 1 U54 RR024386-01A1; received honorarium from NYUSOM; and receives institutional support from NYUCD.
We read the article by Holmes et al. with great interest. [1] Holmes continues his pioneering work [2] and he and his co-authors now address a significant and highly controversial question: Does peripheral inflammation contribute to the progression of Alzheimer disease (AD)? Plasma/serum markers of systemic inflammation such as CRP or proinflammatory cytokines in predicting cognitive decline have been studied. However, Holmes et al. assessed the added effect of acute peripheral inflammatory events to the systemic TNF-alpha on the cognitive decline.
We examined 18 AD patients and 16 cognitively normal subjects (NL) and found that the number of positive IgG antibody tests against periodontopathic bacteria and TNF-alpha level independently associated with clinical AD. [3] The number of positive IgG antibodies to periodontopathic bacteria significantly improved the TNF-alpha classification of clinical AD and NL subjects. These results support Holmes et al.’s findings and suggest that when investigating the role of peripheral inflammation in the progression of AD or cognitive decline, evaluating just plasma/serum proinflammatory markers may not be sufficient. Acute and chronic inflammatory events are highly complex processes and may not be reflected in the value of one specific cytokine.
It is also possible that plasma/serum proinflammatory markers add additional value to the acute/chronic inflammatory events in predicting cognitive decline in NL or AD. Proinflammatory markers such as TNF-alpha represent the ongoing or past inflammatory events and the nature of the host response, whether normal or disregulated. [4]
When evaluating the effect of peripheral inflammations on cognitive decline or AD progression, it is important to combine the inflammatory events with measures of inflammatory response.
References
1. Holmes C, Cunningham C, Zotova E, et al. Systemic inflammation and disease progression in Alzheimer disease. Neurology 2009;73:768-774.
2. Holmes C, El-Okl M, Williams AL, Cunningham C, Wilcockson D, Perry VH. Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease. J Neurol Neurosurg Psychiatry 2003;74:788-789.
3. Kamer AR, Craig RG, Pirraglia E, et al. TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects. J Neuroimmunol. Epub 2009 Sep 19.
4. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol 2009;39:687-699.
Disclosure: Dr. Kamer served as Associate Editor for Journal of Alzheimer’s disease; receives funds from NIH [AG036502-01 (Coinvestigator), NIH/NCRR 1 U54 RR024386-01A1; received honorarium from NYUSOM; and receives institutional support from NYUCD.