European Journal of Neurology 2014, 21: e100
doi:10.1111/ene.12563
LETTER TO THE EDITOR Association between Helicobacter pylori burden and Alzheimer’s disease J. Kountouras, E. Gavalas, S. A. Polyzos, G. Deretzi, G. Kouklakis, S. Grigoriadis, N. Grigoriadis, M. Boziki, C. Zavos, D. Tzilves and P. Katsinelos Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece Correspondence: J. Kountouras, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece (tel.: +30-2310892238; fax: +30-2310-992794; e-mail: [email protected]).
Keywords: Alzheimer’s disease, bacterial infections, cognitive disorders and dementia, infections, mild cognitive impairment, neurological disorders Received: 21 June 2014 Accepted: 2 July 2014 Dear Editor, Bu et al. [1], by using serology, state that infectious burden, including Helicobacter pylori (Hp), is associated with Alzheimer’s disease (AD): infectious burden elevation might directly increase serum beta-amyloid protein, thereby promoting AD development; and infectious burden may contribute to AD pathogenesis via cardiovascular and cerebrovascular diseases and/or neuroinflammation. Regarding Hp infection (Hp-I) burden, it is important to note that the serological method for infection status is inferior to the histological method, the practical diagnostic gold standard of active Hp-I; only active Hp-I induces humoral and
cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with nerve components, thereby affecting neural tissue damage [2]. Moreover, Hp-I eradication might delay AD progression, particularly at early disease stages including mild cognitive impairment. Based on histological analysis for Hp-I documentation, a higher prevalence of Hp-I in AD and mild cognitive impairment patients in a Greek cohort has been found [2,3]; increased cerebrospinal fluid anti-Hp immunoglobulin G antibody levels in AD patients may reflect the disease severity; and Hp eradication may positively influence AD manifestations at 2- and 5-year clinical end-points [4]. Consistent associations with the Greek data were consequently shown in studies from France and in two large-scale epidemiological studies from the USA (one mentioned by the authors [1]) [5], supporting a role for Hp-I in AD pathobiology. In this respect, recent experimental data indicate that intraperitoneal injection of Hp filtrate, but not Escherichia coli, increases Ab42 production by enhancing the activity of c-secretase, thereby inducing cognitive impairment through interrupting the synaptic function [6]. Viewing the aforementioned data, apart from the cardiovascular and cerebrovascular diseases mentioned by the authors [1], Hp might also access brain via the oral-nasal-olfactory pathway or by circulating monocytes (possibly infected with Hp due to defective autophagy) through a disrupted blood brain barrier, leading to AD development and/ or progression [5]; several Hp-induced inflammatory mediators such as tumor necrosis factor a and interleukin 6, also
mentioned by the authors [1], may contribute to blood brain barrier disruption and AD pathogenesis [5]. Likewise, human defensins might contribute to Hp-related AD pathophysiology by modulating innate and adaptive immune system responses [6]. However, further studies are warranted to elucidate these considerations. Disclosure of conflicts of interest The authors declare no financial or other conflicts of interest. References 1. Bu XL, Yao XQ, Jiao SS, et al. A study on the association between infectious burden and Alzheimer’s disease. Eur J Neurol 2014; doi: 10.1111/ene.12477 [Epub ahead of print]. 2. Kountouras J, Tsolaki M, Boziki M, et al. Association between Helicobacter pylori infection and mild cognitive impairment. Eur J Neurol 2007; 14: 976–982. 3. Kountouras J, Tsolaki M, Gavalas E, et al. Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology 2006; 66: 938–940. 4. Kountouras J, Boziki M, Gavalas E, et al. Five-year survival following Helicobacter pylori eradication in Alzheimer’s disease patients. Cogn Behav Neurol 2010; 23: 199– 204. 5. Kountouras J, Deretzi G, Gavalas E, et al. A proposed role of human defensins in Helicobacter pylori-related neurodegenerative disorders. Med Hypotheses 2014; 82: 368– 373. 6. Wang XL, Zeng J, Feng J, et al. Helicobacter pylori filtrate impairs spatial learning and memory in rats and increases b-amyloid by enhancing expression of presenilin2. Front Aging Neurosci 2014; 6: 66.
© 2014 EAN
doi:10.1111/ene.12563
LETTER TO THE EDITOR Association between Helicobacter pylori burden and Alzheimer’s disease J. Kountouras, E. Gavalas, S. A. Polyzos, G. Deretzi, G. Kouklakis, S. Grigoriadis, N. Grigoriadis, M. Boziki, C. Zavos, D. Tzilves and P. Katsinelos Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece Correspondence: J. Kountouras, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece (tel.: +30-2310892238; fax: +30-2310-992794; e-mail: [email protected]).
Keywords: Alzheimer’s disease, bacterial infections, cognitive disorders and dementia, infections, mild cognitive impairment, neurological disorders Received: 21 June 2014 Accepted: 2 July 2014 Dear Editor, Bu et al. [1], by using serology, state that infectious burden, including Helicobacter pylori (Hp), is associated with Alzheimer’s disease (AD): infectious burden elevation might directly increase serum beta-amyloid protein, thereby promoting AD development; and infectious burden may contribute to AD pathogenesis via cardiovascular and cerebrovascular diseases and/or neuroinflammation. Regarding Hp infection (Hp-I) burden, it is important to note that the serological method for infection status is inferior to the histological method, the practical diagnostic gold standard of active Hp-I; only active Hp-I induces humoral and
cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with nerve components, thereby affecting neural tissue damage [2]. Moreover, Hp-I eradication might delay AD progression, particularly at early disease stages including mild cognitive impairment. Based on histological analysis for Hp-I documentation, a higher prevalence of Hp-I in AD and mild cognitive impairment patients in a Greek cohort has been found [2,3]; increased cerebrospinal fluid anti-Hp immunoglobulin G antibody levels in AD patients may reflect the disease severity; and Hp eradication may positively influence AD manifestations at 2- and 5-year clinical end-points [4]. Consistent associations with the Greek data were consequently shown in studies from France and in two large-scale epidemiological studies from the USA (one mentioned by the authors [1]) [5], supporting a role for Hp-I in AD pathobiology. In this respect, recent experimental data indicate that intraperitoneal injection of Hp filtrate, but not Escherichia coli, increases Ab42 production by enhancing the activity of c-secretase, thereby inducing cognitive impairment through interrupting the synaptic function [6]. Viewing the aforementioned data, apart from the cardiovascular and cerebrovascular diseases mentioned by the authors [1], Hp might also access brain via the oral-nasal-olfactory pathway or by circulating monocytes (possibly infected with Hp due to defective autophagy) through a disrupted blood brain barrier, leading to AD development and/ or progression [5]; several Hp-induced inflammatory mediators such as tumor necrosis factor a and interleukin 6, also
mentioned by the authors [1], may contribute to blood brain barrier disruption and AD pathogenesis [5]. Likewise, human defensins might contribute to Hp-related AD pathophysiology by modulating innate and adaptive immune system responses [6]. However, further studies are warranted to elucidate these considerations. Disclosure of conflicts of interest The authors declare no financial or other conflicts of interest. References 1. Bu XL, Yao XQ, Jiao SS, et al. A study on the association between infectious burden and Alzheimer’s disease. Eur J Neurol 2014; doi: 10.1111/ene.12477 [Epub ahead of print]. 2. Kountouras J, Tsolaki M, Boziki M, et al. Association between Helicobacter pylori infection and mild cognitive impairment. Eur J Neurol 2007; 14: 976–982. 3. Kountouras J, Tsolaki M, Gavalas E, et al. Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology 2006; 66: 938–940. 4. Kountouras J, Boziki M, Gavalas E, et al. Five-year survival following Helicobacter pylori eradication in Alzheimer’s disease patients. Cogn Behav Neurol 2010; 23: 199– 204. 5. Kountouras J, Deretzi G, Gavalas E, et al. A proposed role of human defensins in Helicobacter pylori-related neurodegenerative disorders. Med Hypotheses 2014; 82: 368– 373. 6. Wang XL, Zeng J, Feng J, et al. Helicobacter pylori filtrate impairs spatial learning and memory in rats and increases b-amyloid by enhancing expression of presenilin2. Front Aging Neurosci 2014; 6: 66.
© 2014 EAN
