Early‐onset Alzheimer’s disease is related to differential spatial patterns of tau pathology and cognitive impairment

ABSTRACTLittle is known about olfactory identification (OI) function in early-onset Alzheimer’s disease (EOAD) and early-onset mild cognitive impairment (eoMCI) with age of onset <65 years. We aimed to study OI in EOAD compared with eoMCI and age-matched healthy controls (HC). Nineteen EOAD subjects with mild to moderate dementia, 17 with eoMCI, and 21 HC recruited as a convenience sample from memory services were assessed for cognition, behavioral symptoms, and activities for daily living. The OI was tested using the University of Pennsylvania smell identification test (UPSIT). EOAD participants performed worse compared with eoMCI and HC on cognitive tests and OI (p < 0.001). Although eoMCI had poorer cognitive scores compared to HC, they were similar in their OI function. OI correlated with attention (r = 0.494, p = 0.031), executive functions (r = 0.508, p = 0.026), and praxis (r = 0.455, p = 0.05) within the EOAD group. OI impairment was significantly associated with the diagnosis of EOAD versus eoMCI, but not with eoMCI when compared with HC. OI could potentially be useful in differentiating EOAD from eoMCI. Studies with late-life MCI patients showing OI impairment relative to HC may be attributed to a different disease process. Independent replication in a larger sample is needed to validate these findings.

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Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease

Neuropathology and Applied Neurobiology ◽

10.1111/j.1365-2990.2006.00736.x ◽

2006 ◽

Vol 32 (4) ◽

pp. 374-387 ◽

Cited By ~ 23

Author(s):

A.-M. Shiarli ◽

R. Jennings ◽

J. Shi ◽

K. Bailey ◽

Y. Davidson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Early Onset ◽

Frontotemporal Lobar Degeneration ◽

Chromosome 17 ◽

Tau Pathology ◽

Pick Bodies ◽

Early Onset Alzheimer’S Disease

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Raising the bar: a comparative analysis of patients with Early Onset Alzheimer's disease

International Psychogeriatrics ◽

10.1017/s1041610214000064 ◽

2014 ◽

Vol 26 (12) ◽

pp. 2103-2104 ◽

Cited By ~ 3

Author(s):

Tor Atle Rosness ◽

Knut Engedal ◽

Zeina Chemali

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Comparative Analysis ◽

Early Onset ◽

Sample Population ◽

Younger Patients ◽

Dementia Patients ◽

Early Onset Alzheimer’S Disease ◽

Routine Procedures

Early onset Alzheimer's disease (EOAD) poses considerable challenges to physicians both in diagnostics and treatment, to patients and caregivers trying to cope with a debilitating illness at a young age and a healthcare system that is not geared to cater to degenerating illnesses striking young persons (Van Vliet et al., 2012). Routine procedures and screening measures for elderly people possibly stricken by dementia do not assess younger dementia patients in a favourable fashion. Physicians at an outpatient clinic diagnosing elderly patients, with well established standardized cognitive batteries for an older age norm, i.e. above 65 years may have unadjusted assumptions to account for in younger patients with symptoms of EOAD (Smits et al., 2012). Although a common battery of tests is internationally widely applied in the evaluation of cognitive impairment, these tests have not been validated extensively in a sample population of AD under the age of 65.

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Distinct social-behavioral changes in frontotemporal dementia and early onset Alzheimer's disease

PsycEXTRA Dataset ◽

10.1037/e536722014-001 ◽

2014 ◽

Author(s):

Joseph P. Barsuglia ◽

Michelle J. Mather ◽

Hemali V. Panchal ◽

Aditi Joshi ◽

Elvira Jimenez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Early Onset ◽

Behavioral Changes ◽

Early Onset Alzheimer’S Disease

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48-hour Ambulatory EEG Monitoring in Early Onset Alzheimer's Disease

Case Medical Research ◽

10.31525/ct1-nct04002583 ◽

2019 ◽

Author(s):

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Eeg Monitoring ◽

Early Onset Alzheimer’S Disease

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Depressive Symptoms and APOE ε2 Broad the Natural History in Presenilin-1 E280A Familial Early-Onset Alzheimer's Disease

SSRN Electronic Journal ◽

10.2139/ssrn.3284189 ◽

2018 ◽

Author(s):

Natalia Acosta-Baena ◽

Carlos Mario Lopera-Gómez ◽

Mario César Jaramillo-Elorza ◽

Margarita Giraldo-Chica ◽

Mauricio Arcos-Burgos ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Depressive Symptoms ◽

Natural History ◽

Early Onset ◽

Presenilin 1 ◽

Early Onset Alzheimer’S Disease

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Identification of a Pathogenic PSEN1 Ala285Val Mutation Associated with Early-Onset Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205017666200626210727 ◽

2020 ◽

Vol 17 (5) ◽

pp. 438-445

Author(s):

Van Giau Vo ◽

Jung-Min Pyun ◽

Eva Bagyinszky ◽

Seong S.A. An ◽

Sang Y. Kim

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Temporal Lobe ◽

Early Onset ◽

Parietal Lobe ◽

Disease Diagnosis ◽

Random Coil ◽

Magnetic Resonance Imaging Scan ◽

Preclinical Ad ◽

Early Onset Alzheimer’S Disease

Background: Presenilin 1 (PSEN1) was suggested as the most common causative gene of early onset Alzheimer’s Disease (AD). Methods: Patient who presented progressive memory decline in her 40s was enrolled in this study. A broad battery of neuropsychological tests and neuroimaging was applied to make the diagnosis. Genetic tests were performed in the patient to evaluate possible mutations using whole exome sequencing. The pathogenic nature of missense mutation and its 3D protein structure prediction were performed by in silico prediction programs. Results: A pathogenic mutation in PSEN1 (NM_000021.3: c.1027T>C p.Ala285Val), which was found in a Korean EOAD patient. Magnetic resonance imaging scan showed mild left temporal lobe atrophy. Hypometabolism appeared through 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) scanning in bilateral temporal and parietal lobe, and 18F-Florbetaben-PET (FBB-PET) showed increased amyloid deposition in bilateral frontal, parietal, temporal lobe and hence presumed preclinical AD. Protein modeling showed that the p.Ala285Val is located in the random coil region and could result in extra stress in this region, resulting in the replacement of an alanine residue with a valine. This prediction was confirmed previous in vitro studies that the p.Trp165Cys resulted in an elevated Aβ42/Aβ40 ratio in both COS-1 and HEK293 cell lines compared that of wild-type control. Conclusion: Together, the clinical characteristics and the effect of the mutation would facilitate our understanding of PSEN1 in AD pathogenesis for the disease diagnosis and treatment. Future in vivo study is needed to evaluate the role of PSEN1 p.Ala285Val mutation in AD progression.

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