P2-080: Amyloid status and neuropsychological profiles in early-onset, late-onset and very late-onset dementia due to probable Alzheimer's disease

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

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Too narrow and too broad: Differentiating late-onset dementia from its historical entanglement with Alzheimer’s disease

Aging Brain ◽

10.1016/j.nbas.2021.100010 ◽

2021 ◽

Vol 1 ◽

pp. 100010

Author(s):

Kristine F. Moseholm ◽

Karin Tybjerg ◽

Majken K. Jensen ◽

Rudi G.J. Westendorp

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Late Onset ◽

Late Onset Dementia

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The clinical utility of gene testing for Alzheimer’s disease

Neurology International ◽

10.4081/ni.2011.e1 ◽

2011 ◽

Vol 3 (1) ◽

pp. 1 ◽

Cited By ~ 8

Author(s):

Emily R. Atkins ◽

Peter K. Panegyres

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Late Onset ◽

Association Studies ◽

Susceptibility Gene ◽

Genome Wide Association Studies ◽

Apoe Ε4 ◽

Gene Testing ◽

A Genome

Alzheimer’s disease (AD) is the largest cause of dementia, affecting 35.6 million people in 2010. Amyloid precursor protein, presenilin 1 and presenilin 2 mutations are known to cause familial early-onset AD, whereas apolipoprotein E (APOE) ε4 is a susceptibility gene for late-onset AD. The genes for phosphatidylinositol- binding clathrin assembly protein, clusterin and complement receptor 1 have recently been described by genome-wide association studies as potential risk factors for lateonset AD. Also, a genome association study using single neucleotide polymorphisms has identified an association of neuronal sortilin related receptor and late-onset AD. Gene testing, and also predictive gene testing, may be of benefit in suspected familial early-onset AD however it adds little to the diagnosis of lateonset AD and does not alter the treatment. We do not recommend APOE ε4 genotyping.

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Is it Useful to Manage Alzheimer’s Disease as Two Clinical Subtypes: Early Onset and Late Onset Subtypes?

Basic, Clinical, and Therapeutic Aspects of Alzheimer’s and Parkinson’s Diseases - Advances in Behavioral Biology ◽

10.1007/978-1-4684-5847-3_30 ◽

1990 ◽

pp. 143-146

Author(s):

Kazuhiko Kono ◽

Hidetoshi Endo ◽

Takayuki Yamamoto ◽

Fumio Kuzuya

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Late Onset

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HERPESVIRUS INFECTIONS AND CLINICAL-IMMUNOLOGIC INTERACTIONS IN PATIENTS WITH EARLY-ONSET ALZHEIMER’S DISEASE AND LATE-ONSET ALZHEIMER’S DISEASE

Medical Immunology (Russia) ◽

10.15789/1563-0625-hia-2168 ◽

2021 ◽

Vol 23 (4) ◽

pp. 805-812

Author(s):

I. K. Malashenkova ◽

D. P. Ogurtsov ◽

S. A. Krynskiy ◽

N. A. Khailov ◽

N. D. Selezneva ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Viral Load ◽

Early Onset ◽

Late Onset ◽

Adaptive Immune Response ◽

Subsequent Development ◽

Chronic Infections ◽

Immune Parameters ◽

Inflammatory Protein

Alzheimer’s disease (AD) is currently the most common cause of dementia. A significant role in the pathogenesis of AD belongs to the activation of the mechanisms of neuroinflammation. There is a hypothesis that chronic infections may play a role in the maintenance of the inflammatory response in AD. The aim of this work was to study the detection rate and DNA level of herpesviruses, as well as their possible relationship with the level of the key cytokines and with clinical parameters of AD in patients with early and late onset. 30 patients with AD and 33 healthy volunteers were enrolled. The quantitative determination of DNA of CMV, EBV, HHV-6, HHV-7 was carried out by PCR. The level of cytokines and soluble IL-1β antagonist (IL-1ra) in the blood was determined by ELISA. Herpesvirus infection with increased viral load was determined if at least one of the criteria was present: 1) DNA level of EBV and/or HHV-6 > 10,000 copies/ml in saliva; 2) presence of DNA of at least one of the EBV, HHV-6, HHV-7 viruses in the blood. In the subgroup of patients with early onset and increased viral load, there was a higher increase in the levels of a number of cytokines: proinflammatory IL-8 and IL-12, a Th2-cytokine IL-4, a cytokine of the adaptive immune response IL-2. However, the level of the anti-inflammatory protein IL-1ra was lower than in the controls. These changes may indicate a dysregulation of the antiviral response, with a predominance of activation of systemic inflammation and Th2-mediated reactions. Also, in early onset AD the increased viral load was associated with lower scores on Boston naming test. The results indicate that in studies of AD mechanisms and in the search for prognostic markers of the disease, it is important to take into account the heterogeneity of AD in terms of genetic predisposition factors, risk factors, immune parameters and clinical data. Such approach is necessary for the subsequent development of personalized approaches to the prevention and treatment of AD.

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Prevalence and Severity of Neuropsychiatric Symptoms in Early- Versus Late-Onset Alzheimer’s Disease

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317519841191 ◽

2019 ◽

Vol 34 (7-8) ◽

pp. 433-438 ◽

Cited By ~ 2

Author(s):

Sarah Baillon ◽

Amy Gasper ◽

Frances Wilson-Morkeh ◽

Megan Pritchard ◽

Amala Jesu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Late Onset ◽

Functional Dependence ◽

Neuropsychiatric Symptoms ◽

Caregiver Distress ◽

Duration Of Illness ◽

Symptom Prevalence ◽

Early Onset Alzheimer’S Disease

Background: The study aimed to compare neuropsychiatric symptoms (NPS) in people with early-onset Alzheimer’s disease (EOAD) and late-onset AD (LOAD). Methods: Fifty-six participants with LOAD and 24 participants with EOAD having mild dementia were assessed for NPS for their frequency, severity, and caregiver distress as measured by Neuropsychiatry Inventory (NPI) along with assessments of cognition and functional dependence. Results: Participants with EOAD and LOAD were not significantly different for total NPI score ( P = .057). Early-onset Alzheimer disease had greater prevalence of all the NPS except apathy. Participants with EOAD were significantly worse on anxiety ( P = .03), irritability ( P = .01), and sleep ( P < .01) subscales and their carers significantly more distressed by their irritability ( P = .002) and sleeping patterns ( P = .005). Regression analysis showed that higher NPI score was associated with longer duration of illness in EOAD and higher functional dependence in LOAD. Conclusions: The NPS severity was similar between EOAD and LOAD although EOAD had higher symptom prevalence and carer distress.

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Assoziationen zwischen Cholesterin, APOB und früher Alzheimer-Erkrankung

Fortschritte der Neurologie · Psychiatrie ◽

10.1055/a-0987-0793 ◽

2020 ◽

Vol 88 (01) ◽

pp. 4

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Late Onset ◽

Alzheimer Krankheit ◽

Early Onset Alzheimer’S Disease

Hohe Cholesterinwerte sind ein Risikofaktor für die Entwicklung der altersbedingten, späten Form der Alzheimer-Krankheit, der „Late-onset Alzheimer`s disease“ (LOAD). Doch wie die seltenere, frühe Form, die „Early-onset Alzheimer‘s disease“ (EOAD) mit Cholesterin zusammenhängt, war bisher unklar. In dieser Studie untersuchten die Forscher Assoziationen zwischen Cholesterinwerten und EOAD, sowie zugrunde liegende genetische Mechanismen.

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