The clinical phenotype of familial and sporadic late onset Alzheimer's disease

Holmes, Clive; Lovestone, Simon

doi:10.1002/gps.540

Cited by 14 publications

(7 citation statements)

References 17 publications

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“…Familial cases of the disease appear to have the same clinical and pathologic phenotypes as sporadic cases. Notably, a study designed to investigate the existence of specific differences in the clinical features of fAD and sAD revealed that—apart from the age of onset, where a positive family history of dementia was associated with an earlier beginning—no major differences in terms of clinical phenotype—including rate of cognitive decline, duration of illness, and presence of non-cognitive symptoms—were reported between fAD patients compared to patients with sporadic disease [38,39]. In another study, AD patients were examined to test the hypothesis that cases with a familial aggregation differ from cases without such an aggregation with reference to cognitive impairment.…”

Section: Issue 1—the Definition Of the Preclinical Stage Of Admentioning

confidence: 99%

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria

Dubois¹,

Hampel

Feldman

et al. 2016

Alzheimer's & Dementia

1,564

1,200

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During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

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Section: Issue 1—the Definition Of the Preclinical Stage Of Admentioning

confidence: 99%

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria

Dubois¹,

Hampel

Feldman

et al. 2016

Alzheimer's & Dementia

1,564

1,200

View full text Add to dashboard Cite

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Section: The Future: Are We Poised For Success or Failure?mentioning

confidence: 99%

“…But, what if they fail? The effects of FAD mutations are unequivocally to bring forward the age of disease onset: yet, there are little data to support the case that they accelerate the progression of the disease once initiated (Holmes and Lovestone 2002;Godbolt et al 2004;Snider et al 2005;Kumar-Singh et al 2006;Acosta-Baena et al 2011;Karran et al 2011). As FAD mutations likely all increase the probability of amyloid deposition, it could be the case that amyloid deposition triggers, but does not drive, the disease process.…”

Section: What Is the Connection Between Amyloid And Tau Pathologies?mentioning

confidence: 99%

The amyloid cascade hypothesis: are we poised for success or failure?

Karran

Strooper

2016

Journal of Neurochemistry

340

232

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The first description of Alzheimer's disease (AD) was made in 1907 by Alois Alzheimer (Allgemeine Zeitschrift fur Psyciatrie und Psychisch-Gerichtliche Medizin 64, 3, 1907), although other contemporary physicians had made similar, and rather more complete, assessments of the neuropathological changes present in the AD brain (Fischer, Monatsschr Psychiat Neurol 22, 17, 1907). Our knowledge of AD has increased dramatically and continues to accelerate. This year is 25 years after the publication of a series of papers that, in various ways, articulated the amyloid cascade hypothesis (ACH) for AD (Beyreuther and Masters, Brain Pathol 1, 241-251, 1991; Hardy and Allsop, Trends Pharmacol Sci 12, 383-388, 1991; Selkoe, Neuron 6, 487-498, 1991; Hardy and Higgins, Science 256, 184-185, 1992). This review will cover some familiar territory, but we shall also place the ACH into a wider context, compare it with other hypotheses for AD, explore the evolution of the hypothesis to encompass new findings, and determine, irrespective of the merits of the hypothesis itself, whether it has been useful for the research field, both in academia and in industry. Finally, we shall review how the ACH has led to a number of therapeutic approaches, all of which have, to date, failed to reach their primary efficacy end-points in clinical trials and reflect upon what the future may hold.

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“…Mutations in three genes (APP, PSEN1 and PSEN2) are known to cause familial early-onset AD [7][8][9]. Although there is no evidence that autosomal dominant inheritance of mutated genes causes late-onset AD, genetics does appear to play a role in the development of this more common form.…”

Section: Introduction To Alzheimer's Disease (Ad)mentioning

confidence: 97%

Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status

Cai

Innis²,

Pike³

2007

CMC

128

121

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Two of the main pathological hallmarks of Alzheimer's disease (AD) are neuritic plaques and neurofibrillary tangles. Significant evidence supports a critical and probable causative role of amyloid (A ) plaque formation. Since neuroprotective treatments are typically most effective at early stages of injury, the detection and measurement of A load in living brain should be performed at early and perhaps even presymptomatic stages of AD. Two primary targets of molecular imaging research with positron emission tomography (PET) are to develop surrogate markers (radioligands) for assessing disease progression and for monitoring the efficacy of developmental therapeutics. Here, we review the current status of radioligand development for PET imaging of A aggregates. General structure-activity relationships have emerged, including the identification of at least three different ligand binding sites in various A aggregates and recognition of the general structural requirements for ligand binding at each site. Also a few radioligands applicable to imaging A plaques in living human brain with positron emission tomography (PET) have emerged, including [ 11 C]PIB, [ 11 C]SB-13 and [ 18 F]FDDNP.

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The clinical phenotype of familial and sporadic late onset Alzheimer's disease

Abstract: Apart from an earlier age of onset, patients with familial LOAD, as a group, do not have major differences in their clinical phenotype compared to patients with sporadic LOAD.

Cited by 14 publications

References 17 publications

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria

The amyloid cascade hypothesis: are we poised for success or failure?

Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status

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The clinical phenotype of familial and sporadic late onset Alzheimer's disease

Abstract: Apart from an earlier age of onset, patients with familial LOAD, as a group, do not have major differences in their clinical phenotype compared to patients with sporadic LOAD.

Cited by 14 publications

References 17 publications

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria

The amyloid cascade hypothesis: are we poised for success or failure?

Radioligand Development for PET Imaging of &#946;-Amyloid (A&#946;)-Current Status

Contact Info

Product

Resources

About

Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status