Journal of Alzheimer's Disease - Volume 51, issue 4

Authors: Singhrao, Sim K. | Harding, Alice | Chukkapalli, Sasanka | Olsen, Ingar | Kesavalu, Lakshmyya | Crean, StJohn

Article Type: Review Article

Abstract: The primary goal of advancement in clinical services is to provide a health care system that enhances an individual’s quality of life. Incidence of diabetes mellitus, cardiovascular disease, and associated dementia coupled with the advancing age of the population, have led to an increase in the worldwide challenge to the healthcare system. In order to overcome these challenges, prior knowledge of common, reliable risk factors and their effectors is essential. Oral health constitutes one such relatively unexplored but indispensable risk factor for aforementioned co-morbidities, in the form of poor oral hygiene and tooth loss during aging. Behavioral traits such as …low education, smoking, poor diet, neglect of oral health, lack of exercise, and hypertension are few of the risk factors that are shared commonly among these conditions. In addition, common genetic susceptibility traits such as the apolipoprotein E gene, together with an individual’s lifestyle can also influence the development of co-morbidities such as periodontitis, atherosclerosis/stroke, diabetes, and Alzheimer’s disease. This review specifically addresses the susceptibility of apolipoprotein E gene allele 4 as the plausible commonality for the etiology of co-morbidities that eventually result from periodontal diseases and ultimately progress to dementia. Show more

Keywords: Alzheimer’s disease, apolipoprotein, atherosclerosis, co-morbidities, dyslipidemia, periodontitis

DOI: 10.3233/JAD150690

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 935-948, 2016

Authors: Peck, Katlyn J. | Girard, Todd A. | Russo, Frank A. | Fiocco, Alexandra J.

Article Type: Review Article

Abstract: With population aging and a projected exponential expansion of persons diagnosed with Alzheimer’s disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music’s beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion …on the potential underlying mechanisms that may explain music’s beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD. Show more

Keywords: Alzheimer’s disease, autobiographical memory, default network, dopamine, mechanisms, music, sympathetic activity

DOI: 10.3233/JAD-150998

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 949-959, 2016

Authors: Schilling, Melissa A.

Article Type: Research Article

Abstract: Numerous studies have documented a strong association between diabetes and Alzheimer’s disease (AD). The nature of the relationship, however, has remained a puzzle, in part because of seemingly incongruent findings. For example, some studies have concluded that insulin deficiency is primarily at fault, suggesting that intranasal insulin or inhibiting the insulin-degrading enzyme (IDE) could be beneficial. Other research has concluded that hyperinsulinemia is to blame, which implies that intranasal insulin or the inhibition of IDE would exacerbate the disease. Such antithetical conclusions pose a serious obstacle to making progress on treatments. However, careful integration of multiple strands of research, with …attention to the methods used in different studies, makes it possible to disentangle the research on AD. This integration suggests that there is an important relationship between insulin, IDE, and AD that yields multiple pathways to AD depending on the where deficiency or excess in the cycle occurs. I review evidence for each of these pathways here. The results suggest that avoiding excess insulin, and supporting robust IDE levels, could be important ways of preventing and lessening the impact of AD. I also describe what further tests need to be conducted to verify the arguments made in the paper, and their implications for treating AD. Show more

Keywords: Alzheimer disease, amylin, amyloid beta-peptide, dementia, diabetes mellitus, insulin, insulysin, metalloproteases, neprilysin

DOI: 10.3233/JAD-150980

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 961-977, 2016

Authors: Itzhaki, Ruth F. | Lathe, Richard | Balin, Brian J. | Ball, Melvyn J. | Bearer, Elaine L. | Braak, Heiko | Bullido, Maria J. | Carter, Chris | Clerici, Mario | Cosby, S. Louise | Del Tredici, Kelly | Field, Hugh | Fulop, Tamas | Grassi, Claudio | Griffin, W. Sue T. | Haas, Jürgen | Hudson, Alan P. | Kamer, Angela R. | Kell, Douglas B. | Licastro, Federico | Letenneur, Luc | Lövheim, Hugo | Mancuso, Roberta | Miklossy, Judith | Otth, Carola | Palamara, Anna Teresa | Perry, George | Preston, Christopher | Pretorius, Etheresia | Strandberg, Timo | Tabet, Naji | Taylor-Robinson, Simon D. | Whittum-Hudson, Judith A.

Article Type: Editorial

DOI: 10.3233/JAD-160152

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 979-984, 2016

Authors: Lou, Guofeng | Zhang, Qihao | Xiao, Fei | Xiang, Qi | Su, Zhijian | Huang, Yadong

Article Type: Short Communication

Abstract: Neurotoxic amyloid-β (Aβ) peptide causing cognitive function disabilities is one of the most characteristic pathological features in Alzheimer’s disease (AD). A novel fusion protein, TAT-haFGF, was administrated to AβPP/PS1 transgenic mice by intravenous (IV) injection and intranasal (IN) delivery, respectively, for 5 weeks to compare the pharmacodynamics between the two routes of administration. Our results showed that IN administration of TAT-haFGF improved cognition and reduced Aβ plaques more significantly in AβPP/PS1 mice, when compared with IV injection. Our new findings suggest that TAT-haFGF might be a promising new therapy to attenuate AD pathological process.

Keywords: AβPP/PS1, Alzheimer’s disease, haFGF, intranasal administration, TAT

DOI: 10.3233/JAD-151121

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 985-990, 2016

Authors: Remington, Ruth | Bechtel, Cynthia | Larsen, David | Samar, Annemarie | Page, Robert | Morrell, Christopher | Shea, Thomas B.

Article Type: Short Communication

Abstract: Nutritional interventions have shown varied efficacy on cognitive performance during Alzheimer’s disease (AD). Twenty-four individuals diagnosed with AD received a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) under open-label conditions (ClinicalTrials.gov NCT01320527). Primary outcome was cognitive performance. Secondary outcomes were behavioral and psychological symptoms of dementia (BPSD) and activities of daily living. Participants maintained their baseline cognitive performance and BPSD over 12 months. These findings are consistent with improvement in cognitive performance and BPSD in prior placebo-controlled studies with NF, and contrast with the routine decline for participants receiving placebo.

Keywords: Alzheimer’s disease, behavioral symptoms, cognitive performance, mood, nutraceutical formulation

DOI: 10.3233/JAD-151098

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 991-995, 2016

Authors: Sakai, Kazuyoshi | Senda, Takao | Hata, Ryuji | Kuroda, Makoto | Hasegawa, Midori | Kato, Masao | Abe, Masato | Kawaguchi, Kazunori | Nakai, Shigeru | Hiki, Yoshiyuki | Yuzawa, Yukio | Kitaguchi, Nobuya

Article Type: Short Communication

Abstract: As a proof of concept that removal of blood amyloid-β (Aβ) can reduce Aβ deposition in the brains of patients with Alzheimer’s disease, cortices of patients who had undergone hemodialysis (HD), which removes Aβ from the blood, were histochemically analyzed; postmortem brain sections were stained with anti-Aβ antibodies. Brains from patients who had undergone HD had significantly fewer senile plaques than those of patient who had not undergone HD. This significant difference was also confirmed by silver staining. Our findings suggest that removal of blood Aβ by hemodialysis results in lower accumulation of Aβ in the brain.

Keywords: Alzheimer’s disease, amyloid-β (Aβ), Aβ deposition, cerebral cortex, hemodialysis, senile plaque

DOI: 10.3233/JAD-151139

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 997-1002, 2016

Authors: de Pedro-Cuesta, Jesús | Martínez-Martín, Pablo | Rábano, Alberto | Alcalde-Cabero, Enrique | José García López, Fernando | Almazán-Isla, Javier | Ruiz-Tovar, María | Medrano, Maria-José | Avellanal, Fuencisla | Calero, Olga | Calero, Miguel

Article Type: Research Article

Abstract: Background: Sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (NDDs), there was a need to identify specific “drivers”, i.e., risk factors with impact on specific deposits, such as amyloid-β, tau, or α -synuclein, acting across entities. Objectives and Methods: Redefining drivers as “neither protein/gene- nor entity-specific features identifiable in the clinical and general epidemiology of conformational NDDs (CNDDs) as potential footprints of templating/spread/transfer mechanisms”, we conducted an analysis of the epidemiology of ten CNDDs, searching for patterns. Results: We identified seven potential drivers, each of which was shared by at …least two CNDDs: 1) an age-at-exposure-related susceptibility to Creutzfeldt-Jakob disease (CJD) and several late-life CNDDs; 2) a relationship between age at onset, survival, and incidence; 3) shared genetic risk factors for CJD and late-life CNNDs; 4) partly shared personal (diagnostic, educational, behavioral, and social risk factors) predating clinical onset of late-life CNDDs; 5) two environmental risk factors, namely, surgery for sporadic CJD and amyotrophic lateral sclerosis, and Bordetella pertussis infection for Parkinson’s disease; 6) reticulo-endothelial system stressors or general drivers (andropause or premenopausal estrogen deficiency, APOE ɛ 4, and vascular risk factors) for late-life CNDDs such as dementia/Alzheimer’s disease, type-2 diabetes mellitus, and some sporadic cardiac and vascular degenerative diseases; and 7) a high, invariant incidence ratio of sporadic to genetic forms of mid- and late-life CNDDs, and type-2 diabetes mellitus. Conclusion: There might be a systematic epidemiologic pattern induced by specific proteins (PrP, TDP-43, SOD1, α -synuclein, amyloid-β, tau, Langerhans islet peptide, and transthyretin) or established combinations of these. Show more

Keywords: Amyloid, epidemiology, methods, neurodegeneration, risk factors

DOI: 10.3233/JAD-150884

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 1003-1022, 2016

Authors: Pluta, Ryszard | Kocki, Janusz | Ułamek-Kozioł, Marzena | Petniak, Alicja | Gil-Kulik, Paulina | Januszewski, Sławomir | Bogucki, Jacek | Jabłoński, Mirosław | Brzozowska, Judyta | Furmaga-Jabłońska, Wanda | Bogucka-Kocka, Anna | Czuczwar, Stanisław J.

Article Type: Research Article

Abstract: Brain ischemia may be causally related with Alzheimer’s disease. Presumably, β-secretase and amyloid-β protein precursor gene expression changes may be associated with Alzheimer’s disease neuropathology. Consequently, we have examined quantitative changes in both β-secretase and amyloid-β protein precursor genes in the medial temporal lobe cortex with the use of quantitative rtPCR analysis following 10-min global brain ischemia in rats with survival of 2, 7, and 30 days. The greatest significant overexpression of β-secretase gene was noted on the 2nd day, while on days 7–30 the expression of this gene was only modestly downregulated. Amyloid-β protein precursor gene was downregulated on …the 2nd day, but on days 7–30 postischemia, there was a significant reverse tendency. Thus, the demonstrated alterations indicate that the considerable changes of expression of β-secretase and amyloid-β protein precursor genes may be connected with a response of neurons in medial temporal lobe cortex to transient global brain ischemia. Finally, the ischemia-induced gene changes may play a key role in a late and slow onset of Alzheimer-type pathology. Show more

Keywords: Alzheimer’s disease, amyloid-β protein precursor, β-secretase, brain ischemia, dementia, temporal cortex

DOI: 10.3233/JAD-151102

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 1023-1031, 2016

Authors: Barthélemy, Nicolas R. | Gabelle, Audrey | Hirtz, Christophe | Fenaille, François | Sergeant, Nicolas | Schraen-Maschke, Susanna | Vialaret, Jérôme | Buée, Luc | Junot, Christophe | Becher, François | Lehmann, Sylvain

Article Type: Research Article

Abstract: Microtubule-associated Tau proteins are major actors in neurological disorders, the so-called tauopathies. In some of them, and specifically in Alzheimer’s disease (AD), hyperphosphorylated forms of Tau aggregate into neurofibrillary tangles. Following and understanding the complexity of Tau’s molecular profile with its multiple isoforms and post-translational modifications represent an important issue, and a major analytical challenge. Immunodetection methods are, in fact, limited by the number, specificity, sensitivity, and capturing property of the available antibodies. Mass spectrometry (MS) has recently allowed protein quantification in complex biological fluids using isotope-labeled recombinant standard for absolute quantification (PSAQ). To study Tau proteins, which are found …at very low concentrations within the cerebrospinal fluid (CSF), we relied on an innovative two-step pre-fractionation strategy, which was not dependent on immuno-enrichment. We then developed a sensitive multiplex peptide detection capability using targeted high-resolution MS to quantify Tau-specific peptides covering its entire sequence. This approach was used on a clinical cohort of patients with AD, progressive supranuclear palsy (PSP), and dementia with Lewy body (DLB) and with control non-neurodegenerative disorders. We uncovered a common CSF Tau molecular profile characterized by a predominance of central core expression and 1N/3R isoform detection. While PSP and DLB tau profiles showed minimal changes, AD was characterized by a unique pattern with specific modifications of peptide distribution. Taken together these results provide important information on Tau biology for future therapeutic interventions, and improved molecular diagnosis of tauopathies. Show more

Keywords: Cerebrospinal fluid, mass spectrometry, neurodegenerative disease, tau protein

DOI: 10.3233/JAD-150962

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 1033-1043, 2016