Journal of Alzheimer's Disease - Volume 62, issue 3

Authors: Perry, George | Avila, Jesus | Tabaton, Massimo | Zhu, Xiongwei

Article Type: Other

DOI: 10.3233/JAD-180120

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 901-901, 2018

Authors: Nacmias, Benedetta | Bagnoli, Silvia | Piaceri, Irene | Sorbi, Sandro

Article Type: Review Article

Abstract: Studies on the genetics of Alzheimer’s disease (AD) have revealed the complexity and heterogeneity of the disease. All our studies have supported this evidence and contribute to the current understanding of the genetic architecture of AD. This report reviews the success of our investigations, focusing on the implications and importance of the genetics of AD, and demonstrates the relevance of research strategies embracing partnerships.

Keywords: Alzheimer‘s disease, autosomal dominant, genetic mutation, genetic risk factor

DOI: 10.3233/JAD-170570

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 903-911, 2018

Authors: Fenoglio, Chiara | Scarpini, Elio | Serpente, Maria | Galimberti, Daniela

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) and frontotemporal dementia (FTD) represent the first cause of dementia in senile and pre-senile population, respectively. A percentage of cases have a genetic cause, inherited with an autosomal dominant pattern of transmission. The majority of cases, however, derive from complex interactions between a number of genetic and environmental factors. Gene variants may act as risk or protective factors. Their combination with a variety of environmental exposures may result in increased susceptibility to these diseases or may influence their course. The scenario is even more complicated considering the effect of epigenetics, which encompasses mechanisms able to alter the …expression of genes without altering the DNA sequence. In this review, an overview of the current genetic and epigenetic progresses in AD and FTD will be provided, with particular focus on 1) causative genes, 2) genetic risk factors and disease modifiers, and 3) epigenetics, including methylation, non-coding RNAs and chromatin remodeling. Show more

Keywords: Alzheimer’s disease, epigenetics, frontotemporal dementia, genetics

DOI: 10.3233/JAD-170702

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 913-932, 2018

Authors: Qiu, Chengxuan | Fratiglioni, Laura

Article Type: Review Article

Abstract: Both the incidence and the prevalence of dementia increase exponentially with increasing age. This raises the question of whether dementia is an inevitable consequence of aging or whether aging without dementia is achievable. In this review article, we sought to summarize the current evidence from epidemiological and neuropathological studies that investigated this topic. Epidemiological studies have shown that dementia could be avoided even at extreme old ages (e.g., centenarians or supercentenarians). Furthermore, clinico-neuropathological studies found that nearly half of centenarians with dementia did not have sufficient brain pathology to explain their cognitive symptoms, while intermediate-to-high Alzheimer pathology was present in …around one-third of very old people without dementia or cognitive impairment. This suggests that certain compensatory mechanisms (e.g., cognitive reserve or resilience) may play a role in helping people in extreme old ages escape dementia syndrome. Finally, evidence has been accumulating in recent years indicating that the incidence of dementia has declined in Europe and North America, which supports the view that the risk of dementia in late life is modifiable. Evidence has emerged that intervention strategies that promote general health, maintain vascular health, and increase cognitive reserve are likely to help preserve cognitive function till late life, thus achieving the goal of aging without dementia. Show more

Keywords: Aging, Alzheimer’s disease, centenarians, dementia, epidemiology, interventions

DOI: 10.3233/JAD-171037

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 933-942, 2018

Authors: Griñán-Ferré, Christian | Corpas, Rubén | Puigoriol-Illamola, Dolors | Palomera-Ávalos, Verónica | Sanfeliu, Coral | Pallàs, Mercè

Article Type: Review Article

Abstract: Epigenetics is emerging as the missing link among genetic inheritance, environmental influences, and body and brain health status. In the brain, specific changes in nucleic acids or their associated proteins in neurons and glial cells might imprint differential patterns of gene activation that will favor either cognitive enhancement or cognitive loss for more than one generation. Furthermore, derangement of age-related epigenetic signaling is appearing as a significant risk factor for illnesses of aging, including neurodegeneration and Alzheimer’s disease (AD). In addition, better knowledge of epigenetic mechanisms might provide hints and clues in the triggering and progression of AD. Intense research …in experimental models suggests that molecular interventions for modulating epigenetic mechanisms might have therapeutic applications to promote cognitive maintenance through an advanced age. The SAMP8 mouse is a senescence model with AD traits in which the study of epigenetic alterations may unveil epigenetic therapies against the AD. Show more

Keywords: Aging, DNA methylation, epigenetics, histone modification, neurodegeneration

DOI: 10.3233/JAD-170664

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 943-963, 2018

Authors: Martins, Ralph N. | Villemagne, Victor | Sohrabi, Hamid R. | Chatterjee, Pratishtha | Shah, Tejal M. | Verdile, Giuseppe | Fraser, Paul | Taddei, Kevin | Gupta, Veer B. | Rainey-Smith, Stephanie R. | Hone, Eugene | Pedrini, Steve | Lim, Wei Ling | Martins, Ian | Frost, Shaun | Gupta, Sunil | O’Bryant, Sid | Rembach, Alan | Ames, David | Ellis, Kathryn | Fuller, Stephanie J. | Brown, Belinda | Gardener, Samantha L. | Fernando, Binosha | Bharadwaj, Prashant | Burnham, Samantha | Laws, Simon M. | Barron, Anna M. | Goozee, Kathryn | Wahjoepramono, Eka J. | Asih, Prita R. | Doecke, James D. | Salvado, Olivier | Bush, Ashley I. | Rowe, Christopher C. | Gandy, Samuel E. | Masters, Colin L.

Article Type: Review Article

Abstract: Worldwide there are over 46 million people living with dementia, and this number is expected to double every 20 years reaching about 131 million by 2050. The cost to the community and government health systems, as well as the stress on families and carers is incalculable. Over three decades of research into this disease have been undertaken by several research groups in Australia, including work by our original research group in Western Australia which was involved in the discovery and sequencing of the amyloid-β peptide (also known as Aβ or A4 peptide) extracted from cerebral amyloid plaques. This review discusses …the journey from the discovery of the Aβ peptide in Alzheimer’s disease (AD) brain to the establishment of pre-clinical AD using PET amyloid tracers, a method now serving as the gold standard for developing peripheral diagnostic approaches in the blood and the eye. The latter developments for early diagnosis have been largely achieved through the establishment of the Australian Imaging Biomarker and Lifestyle research group that has followed 1,100 Australians for 11 years. AIBL has also been instrumental in providing insight into the role of the major genetic risk factor apolipoprotein E ɛ 4, as well as better understanding the role of lifestyle factors particularly diet, physical activity and sleep to cognitive decline and the accumulation of cerebral Aβ. Show more

Keywords: Aβ, Alzheimer’s disease, amyloid, apolipoprotein E, biomarker, dementia, early diagnosis, preclinical

DOI: 10.3233/JAD-171145

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 965-992, 2018

Authors: Panza, Francesco | Lozupone, Madia | Solfrizzi, Vincenzo | Sardone, Rodolfo | Dibello, Vittorio | Di Lena, Luca | D’Urso, Francesca | Stallone, Roberta | Petruzzi, Massimo | Giannelli, Gianluigi | Quaranta, Nicola | Bellomo, Antonello | Greco, Antonio | Daniele, Antonio | Seripa, Davide | Logroscino, Giancarlo

Article Type: Review Article

Abstract: Frailty, a critical intermediate status of the aging process that is at increased risk for negative health-related events, includes physical, cognitive, and psychosocial domains or phenotypes. Cognitive frailty is a condition recently defined by operationalized criteria describing coexisting physical frailty and mild cognitive impairment (MCI), with two proposed subtypes: potentially reversible cognitive frailty (physical frailty/MCI) and reversible cognitive frailty (physical frailty/pre-MCI subjective cognitive decline). In the present article, we reviewed the framework for the definition, different models, and the current epidemiology of cognitive frailty, also describing neurobiological mechanisms, and exploring the possible prevention of the cognitive frailty progression. Several studies …suggested a relevant heterogeneity with prevalence estimates ranging 1.0–22.0% (10.7–22.0% in clinical-based settings and 1.0–4.4% in population-based settings). Cross-sectional and longitudinal population-based studies showed that different cognitive frailty models may be associated with increased risk of functional disability, worsened quality of life, hospitalization, mortality, incidence of dementia, vascular dementia, and neurocognitive disorders. The operationalization of clinical constructs based on cognitive impairment related to physical causes (physical frailty, motor function decline, or other physical factors) appears to be interesting for dementia secondary prevention given the increased risk for progression to dementia of these clinical entities. Multidomain interventions have the potential to be effective in preventing cognitive frailty. In the near future, we need to establish more reliable clinical and research criteria, using different operational definitions for frailty and cognitive impairment, and useful clinical, biological, and imaging markers to implement intervention programs targeted to improve frailty, so preventing also late-life cognitive disorders. Show more

Keywords: Alzheimer’s disease, biomarkers, dementia, frailty, lifestyle, mild cognitive impairment, nutrition, prevention, subjective cognitive decline, vascular dementia

DOI: 10.3233/JAD-170963

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 993-1012, 2018

Authors: Fiala, Milan | Restrepo, Lucas | Pellegrini, Matteo

Article Type: Review Article

Abstract: This article reviews the basic tenets of a clinical approach to effective immunotherapy of Alzheimer’s disease (AD) in patients with mild cognitive impairment (MCI). Although one randomized controlled study in early MCI patients by fish-derived omega-3 fatty acids (ω -3) showed slowing of disease progression, large clinical trials with different products have failed to show cognitive effects. Macrophages of healthy subjects phagocytize and degrade amyloid-β1 - 42 (Aβ) in the brain tissues, whereas macrophages of patients with AD and MCI are functionally defective. ω -3 and ω -3-derived specialized proresolving mediators (SPMs), such as resolvin D1, have powerful biochemical and immunological …effects, which may repair the functions of MCI patients’ macrophages in the brain’s clearance of Aβ. Unfortunately, ω -3 products on the market have a variable quality. Nutritional supplementation with a combination drink called Smartfish with an emulsion of ω -3 and other fatty acids, antioxidants, 1,25-dihydroxy vitamin D3, and resveratrol improved the innate immune system of MCI patients by modulation of macrophage type to the pro-phagocytic M1-M2 type with an effective unfolded protein response against endoplasmic reticulum stress. Some MCI patients maintained their initial cognitive status for three years on Smartfish supplementation. Future randomized clinical trials should investigate the immune effects of ω -3, 1,25-dihydroxy vitamin D3, and SPMs on macrophage type, function, and biochemistry in parallel with cognitive effects. Show more

Keywords: 1, 25-dihydroxy vitamin D3, amyloid-β, macrophage, mild cognitive impairment, omega-3, unfolded protein response

DOI: 10.3233/JAD-170579

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 1013-1022, 2018

Authors: Ferrer, Isidro

Article Type: Research Article

Abstract: The study of life and living organisms and the way in which these interact and organize to form social communities have been central to my career. I have been fascinated by biology, neurology, and neuropathology, but also by history, sociology, and art. Certain current historical, political, and social events, some occurring proximally but others affecting people in apparently distant places, have had an impact on me. Epicurus, Seneca, and Camus shared their philosophical positions which I learned from. Many scientists from various disciplines have been exciting sources of knowledge as well. I have created a world of hypothesis and experiments …but I have also got carried away by serendipity following unexpected observations. It has not been an easy path; errors and wanderings are not uncommon, and opponents close to home much more abundant than one might imagine. Ambition, imagination, resilience, and endurance have been useful in moving ahead in response to setbacks. In the end, I have enjoyed my dedication to science and I am grateful to have glimpsed beauty in it. These are brief memories of a Spanish neuropathologist born and raised in Barcelona, EU. Show more

Keywords: Neuropathology

DOI: 10.3233/JAD-170609

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 1023-1047, 2018

Authors: Shea, Thomas B.

Article Type: Research Article

Abstract: Turns out I have been a major contributor to the Journal of Alzheimer ’s Disease over its 20-year history. As such, I was invited to provide a review of my work over the years. What follows is a retrospective of how the Alzheimer-related research of a Ph.D. (i.e., not an M.D.) transitioned from basic to clinical, and moved from bench to bedside and back again.I have included some of the more humorous and poignant twists along the way that some older players may find familiar and I hope might inspire some younger players to hang in there.

Keywords: Environmental toxins, methionine cycle, nutrition, oxidative damage, translational studies, traumatic brain injury

DOI: 10.3233/JAD-170724

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 1049-1057, 2018