Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation

Ringman, John M.; Gylys, Karen H.; Medina, Luis D.; Fox, Michelle; Kepe, Vladimir; Flores, Deborah; Apostolova, Liana G.; Barrio, Jorge R.; Small, Gary W.; Silverman, Daniel; Siu, Erin; Cederbaum, Stephen D.; Hečimović, Silva; Malnar, Martina; Chakraverty, Suma; Goate, Alison M.; Bird, Thomas D.; Leverenz, James B.

doi:10.1016/j.neulet.2010.10.039

Cited by 36 publications

(35 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hallucinations and delusions were reported more frequently in PSEN1 A79V MCs from this family, as has been noted previously in individuals with ADAD. 44,45 These findings demonstrate that the clinical phenotypes of late-onset ADAD and LOAD can overlap, and suggest that previously reported clinical (e.g., seizures, early myoclonus, spastic paraparesis, dysarthria, and rapid decline [9][10][11][12][13][14][15][16][17][18] ) and neuropathological differences (e.g., altered cerebral Aβ 42 and neurofibrillary tangle deposition, increased prevalence of cerebral amyloid angiopathy, and formation of "cotton wool" plaques 6,12,16,[19][20][21][22][23][24][25][26][27] ) may reflect age-or mutation-dependent effects.…”

Section: Discussionsupporting

confidence: 63%

“…7,8 Also, ADAD may be characterized by clinical features that are unusual in LOAD, including pyramidal signs, hypo/hyperkinetic movement disorders, ataxia, and early myoclonus and seizures. [9][10][11][12][13][14][15][16][17][18] Additional differences in the pattern of cerebral Aβ 42 deposition are reported in some ADAD cases, including 6,16,19,20 higher Aβ 42 burden and greater densities of neurofibrillary tangles; [21][22][23] increased Aβ 42 deposition within the cerebellum [24][25][26] and basal ganglia; 19,20 ; and higher prevalence of cerebral amyloid angiopathy and large diffuse so-called "cotton wool" plaques. 12,22,24,27 Such clinical and pathological differences may challenge whether findings from studies of early-onset ADAD, including current trials of anti-amyloid therapies, 28 can be extrapolated to the understanding of the far more common LOAD.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

P2‐203: Phenotypic Similarities between Late‐Onset Autosomal Dominant and Sporadic Alzheimer Disease: A Single‐Family Case‐Control Study

Day

Musiek

Roe

et al. 2016

Alzheimer's & Dementia

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

P2‐203: Phenotypic Similarities between Late‐Onset Autosomal Dominant and Sporadic Alzheimer Disease: A Single‐Family Case‐Control Study

Day

Musiek

Roe

et al. 2016

Alzheimer's & Dementia

Self Cite

View full text Add to dashboard Cite

“…In both symptomatic and presymptomatic APP , PSEN1 and PSEN2 mutation carriers, the majority of the studies found a decrease in Aβ 42 and an increase in both t-tau and p-tau levels when compared with healthy control individuals, consistent with a typical AD profile [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26] (table 1). In some cases, 1 or more markers were found to be unchanged compared to controls [27,28,29,30].…”

Section: Resultsmentioning

confidence: 99%

Cerebrospinal Fluid Biomarkers in Familial Forms of Alzheimer's Disease and Frontotemporal Dementia

Rostgaard

Waldemar

Nielsen

et al. 2015

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

As dementia is a fast-growing health care problem, it is becoming an increasingly urgent need to provide an early diagnosis in order to offer patients the best medical treatment and care. Validated biomarkers which reflect the pathology and disease progression are essential for diagnosis and are important when developing new therapies. Today, the core protein biomarkers amyloid-β₄₂, total tau and phosphorylated tau in the cerebrospinal fluid (CSF) are used to diagnose Alzheimer's disease (AD), because these biomarkers have shown to reflect the underlying amyloid and tau pathology. However, the biomarkers have proved insufficient predictors of dementias with a different pathology, e.g. frontotemporal dementia (FTD); furthermore, the biomarkers are not useful for early AD diagnosis. Familial dementias with a known disease-causing mutation can be extremely valuable to study; yet the biomarker profiles in patients with familial dementias are not clear. This review summarizes CSF biomarker findings from studies on symptomatic and presymptomatic individuals carrying a mutation in one of the genes known to cause early-onset familial AD or FTD. In conclusion, the biomarker profile of inherited AD is quite similar between carriers of different mutations as well as similar to the profile found in sporadic AD, whereas familial FTD does not seem to have a clear biomarker profile. Hence, new biomarkers are needed for FTD.

show abstract

“…The neuropathological changes in FAD are generally similar to those in sporadic AD,3 but atypical neuropathology has been reported in some cases, including the presence of ‘cotton wool’ plaques in the cerebral cortex, non-neuritic amyloid plaques in the cerebellum and degeneration of corticospinal tracts and the basal ganglia 3 5 6. In-vivo neuroimaging studies of FAD mutation carriers show reduced temporal lobe and hippocampal volumes before the onset of symptoms 7.…”

Section: Introductionmentioning

confidence: 82%

“…Analyses of these subjects’ MRI scans have previously been published 6 10 25. High-resolution T1-weighted three-dimensional (3D) images were acquired in the sagittal plane using an MPRAGE sequence (TR=1900 ms, TE=4.38 ms, TI=1100 ms, flip angle 15°, voxel size 1×1×1 mm 3 ).…”

Section: Methodsmentioning

confidence: 99%

Regional brain volume differences in symptomatic and presymptomatic carriers of familial Alzheimer's disease mutations

Lee

Medina

et al. 2012

J Neurol Neurosurg Psychiatry

View full text Add to dashboard Cite

Background Mutations in the presenilin (PSEN1, PSEN2) and amyloid precursor protein (APP) genes cause familial Alzheimer’s disease (FAD) in a nearly fully penetrant, autosomal dominant manner, providing a unique opportunity to study presymptomatic individuals who can be predicted to develop Alzheimer’s disease (AD) with essentially 100% certainty. Using tensor-based morphometry (TBM), we examined brain volume differences between presymptomatic and symptomatic FAD mutation carriers and non-carrier (NC) relatives. Methods Twenty-five mutation carriers and 10 NC relatives underwent brain MRI and clinical assessment. Four mutation carriers had dementia (MUT-Dem), 12 had amnestic mild cognitive impairment (MUT-aMCI) and nine were cognitively normal (MUT-Norm). TBM brain volume maps of MUT-Norm, MUT-aMCI and MUT-Dem subjects were compared to NC subjects. Results MUT-Norm subjects exhibited significantly smaller volumes in the thalamus, caudate and putamen. MUT-aMCI subjects had smaller volumes in the thalamus, splenium and pons, but not in the caudate or putamen. MUT-Dem subjects demonstrated smaller volumes in temporal, parietal and left frontal regions. As non-demented carriers approached the expected age of dementia diagnosis, this was associated with larger ventricular and caudate volumes and a trend towards smaller temporal lobe volume. Conclusions Cognitively intact FAD mutation carriers had lower thalamic, caudate and putamen volumes, and we found preliminary evidence for increasing caudate size during the predementia stage. These regions may be affected earliest during prodromal stages of FAD, while cortical atrophy may occur in later stages, when carriers show cognitive deficits. Further studies of this population will help us understand the progression of neurobiological changes in AD.

show abstract

Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation

Abstract: Background-Familial Alzheimer's disease (AD) due to PSEN1 mutations provides an opportunity to examine AD biomarkers in persons in whom the diagnosis is certain.

Cited by 36 publications

References 20 publications

P2‐203: Phenotypic Similarities between Late‐Onset Autosomal Dominant and Sporadic Alzheimer Disease: A Single‐Family Case‐Control Study

P2‐203: Phenotypic Similarities between Late‐Onset Autosomal Dominant and Sporadic Alzheimer Disease: A Single‐Family Case‐Control Study

Cerebrospinal Fluid Biomarkers in Familial Forms of Alzheimer's Disease and Frontotemporal Dementia

Regional brain volume differences in symptomatic and presymptomatic carriers of familial Alzheimer's disease mutations

Contact Info

Product

Resources

About