“…2) of 603 individuals primarily without dementia, we detected HSV in brain tissue of 11 (1.9%) of the 584 cases from which it was possible to extract DNA. Our serological analyses of 141 cases revealed 85.8% carrying HSV, which is slightly lower than – although in line with – previous epidemiological studies of the virus' presence (Lövheim et al, 2015a,b; Smith and Robinson, 2002). Fig.…”
Section: Discussionsupporting
confidence: 90%
“…tested positive in two or more PCR analyses) were 6/11 (54.5%) compared with 30.2% among those who were HSV-DNA-negative ( P =0.101), 16.7% of those with AD had HSV DNA present in brain tissue compared with 1.8% of non-demented cases ( P =0.113), and anti-HSV sero-positivity was close to being significantly associated with an increased risk of Aβ aggregations ( P =0.052). These results are not in disagreement with previous studies suggesting that Aβ aggregations and/or AD are associated with HSV (Ball, 1982; Itzhaki, 2014; Itzhaki et al, 2016; Letenneur et al, 2008; Lövheim et al, 2015a,b; Steel and Eslick, 2015), but should be confirmed in larger studies. However, most of the individuals that had Aβ aggregations did not have detectable HSV DNA in brain tissue.…”
Section: Discussioncontrasting
confidence: 51%
“…In addition, the rare HSE affects similar brain regions to those seen in AD (Ball, 1982). In recent years, evidence for HSV as a possible cause of AD has accumulated, and is supported by epidemiological (Letenneur et al, 2008; Lövheim et al, 2015a,b), neuropathological (Steel and Eslick, 2015; Wozniak et al, 2009), as well as in vitro data demonstrating AD-specific changes in neural cells following HSV infection (Santana et al, 2012). …”
Herpes simplex virus (HSV) type 1 affects a majority of the population and recent evidence suggests involvement in Alzheimer's disease aetiology. We investigated the prevalence of HSV type 1 and 2 in the Tampere Autopsy Study (TASTY) brain samples using PCR and sero-positivity in plasma, and associations with Alzheimer's disease neuropathology. HSV was shown to be present in human brain tissue in 11/584 (1.9%) of samples in the TASTY cohort, of which six had Alzheimer's disease neuropathological amyloid beta (Aβ) aggregations. Additionally, serological data revealed 86% of serum samples tested were IgG-positive for HSV. In conclusion, we report epidemiological evidence of the presence of HSV in brain tissue free from encephalitis symptoms in a cohort most closely representing the general population (a minimum prevalence of 1.9%). Whereas 6/11 samples with HSV DNA in the brain tissue had Aβ aggregations, most of those with Aβ aggregations did not have HSV present in the brain tissue.
“…2) of 603 individuals primarily without dementia, we detected HSV in brain tissue of 11 (1.9%) of the 584 cases from which it was possible to extract DNA. Our serological analyses of 141 cases revealed 85.8% carrying HSV, which is slightly lower than – although in line with – previous epidemiological studies of the virus' presence (Lövheim et al, 2015a,b; Smith and Robinson, 2002). Fig.…”
Section: Discussionsupporting
confidence: 90%
“…tested positive in two or more PCR analyses) were 6/11 (54.5%) compared with 30.2% among those who were HSV-DNA-negative ( P =0.101), 16.7% of those with AD had HSV DNA present in brain tissue compared with 1.8% of non-demented cases ( P =0.113), and anti-HSV sero-positivity was close to being significantly associated with an increased risk of Aβ aggregations ( P =0.052). These results are not in disagreement with previous studies suggesting that Aβ aggregations and/or AD are associated with HSV (Ball, 1982; Itzhaki, 2014; Itzhaki et al, 2016; Letenneur et al, 2008; Lövheim et al, 2015a,b; Steel and Eslick, 2015), but should be confirmed in larger studies. However, most of the individuals that had Aβ aggregations did not have detectable HSV DNA in brain tissue.…”
Section: Discussioncontrasting
confidence: 51%
“…In addition, the rare HSE affects similar brain regions to those seen in AD (Ball, 1982). In recent years, evidence for HSV as a possible cause of AD has accumulated, and is supported by epidemiological (Letenneur et al, 2008; Lövheim et al, 2015a,b), neuropathological (Steel and Eslick, 2015; Wozniak et al, 2009), as well as in vitro data demonstrating AD-specific changes in neural cells following HSV infection (Santana et al, 2012). …”
Herpes simplex virus (HSV) type 1 affects a majority of the population and recent evidence suggests involvement in Alzheimer's disease aetiology. We investigated the prevalence of HSV type 1 and 2 in the Tampere Autopsy Study (TASTY) brain samples using PCR and sero-positivity in plasma, and associations with Alzheimer's disease neuropathology. HSV was shown to be present in human brain tissue in 11/584 (1.9%) of samples in the TASTY cohort, of which six had Alzheimer's disease neuropathological amyloid beta (Aβ) aggregations. Additionally, serological data revealed 86% of serum samples tested were IgG-positive for HSV. In conclusion, we report epidemiological evidence of the presence of HSV in brain tissue free from encephalitis symptoms in a cohort most closely representing the general population (a minimum prevalence of 1.9%). Whereas 6/11 samples with HSV DNA in the brain tissue had Aβ aggregations, most of those with Aβ aggregations did not have HSV present in the brain tissue.
“…Moreover, a recent Sweden longitudinal nested study showed a significant association of HSV-1 infection with AD risk [18], since elevated anti-HSV-1 antibody levels were found in AD patients [18]. A different study from Italy found that increased serum HSV-1 antibody titers correlated with MRI cortical grey matter volume [19].…”
IntroductionAlzheimer's disease (AD) is the leading cause of dementia in the elderly. Prevalence and incidence of this type of dementia is increasing and extensive research has focused on AD pathogenetic mechanisms to find effective preventive procedures and therapeutic drugs. However, no therapy is available. Therefore, focusing upon diverse aspects of the disease in order to discover new therapeutic strategies appears to be relevant for patients. Moreover, new approaches to the disease's pathogenesis may open innovative prevention opportunities for the elderly or other groups of people without manifest cognitive alterations, but with increased risk of developing dementia.Brain amyloid deposits and intra neuronal neurofibrillary tangles (NFTs) have been suggested as inducers of the disease [1,2]. However, these neuropathological alterations are often also present in the brain of elderly without cognitive alterations or AD pathology [3]. Therefore, it is uncertain whether amyloid or other proteinaceous brain depositions might be causatively linked to AD.The biological role of the amyloid precursor protein (APP) and its proteolytic derivatives (A-beta peptide) in normal brain is still uncertain [4]. However, recent data showed that A-beta peptide is an anti-microbial factor [5]. A recent study reported that the A-beta peptide showed an in vitro anti-virus activity [6]. Therefore, A-beta peptides may play multiple roles in human brain and contribute to antimicroorganism responses.As we elsewhere discussed, genetic data from four genome wide association (GWA) studies on AD [7][8][9] suggested that persistent virus infections may be potentially associated with the age related cognitive decline. In fact, this specific genetic signature may predispose to AD by affecting the individual susceptibility to virus infections [7] during the age associated decline of immune competence.
Adults with Down's syndrome (DS) o trisomy of chromosome 21show an elevated risk of cognitive decline and dementia with advancing age. The over expression of the APP gene on the chromosome 21 may lead to an early amyloid deposition in DS brains and be a susceptibility factor for AD [10].Middle age people with DS also show increased tangle brain deposition, neuronal loss and neuro-inflammation along with cerebrovascular pathology [10]. All these factors might accelerate brain aging in DS. A dramatic increase in life expectancy, coupled with a significant reduction in early mortality, has led to a substantial increment in the number of DS subjects reaching old age. This demographic picture parallels increased incidence and prevalence of the age related degenerative diseases in persons with DS.Chronic inflammation is associated with the pathogenesis of most chronic degenerative diseases. In fact, a relevant inflammatory component is always associated with AD, autoimmune diseases, diabetes, atherosclerosis, sarcopenia and cancer. It is of interest that increased levels of circulating inflammatory mediators may be secondary to impaired cytokine resp...
“…8 Herpes Simplex Virus-1 has also shown some association. 9 Down's syndrome and presence of Pre-Senilin gene are other risk factors. 10 Various hypotheses have been proposed for Alzheimer's disease.…”
Alzheimer's disease, the most common cause of dementia is not a normal part of aging and worsens over time. The most common early symptom of Alzheimer's is difficulty remembering newly learned information. Microscopic changes in the brain begin long before the first signs of memory loss. Two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells. Currently, there are five FDA-approved drugs that treat the symptoms of Alzheimer's diseasetemporarily helping memory and thinking problems in about half of the people who take them. But these medications do not treat the underlying causes of Alzheimer's. In contrast, many of the new drugs in development aim to modify the disease process itself, by impacting one or more of the many wide-ranging brain changes that Alzheimer's causes. These changes offer potential "targets" for new drugs to stop or slow the progress of the disease. Today, there is a worldwide effort under way to find better ways to treat the disease, delay its onset, and prevent it from developing. The current review looks into the current drug therapy for Alzheimer's disease and the ongoing research into new drug targets which could treat the underlying pathology.
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