Longitudinal Observation of Early-Onset Alzheimer’s Disease Dementia with Positive CSF Biomarkers/Negative Amyloid-β Positron-Emission Tomography

We report a 61-year-old woman with clinical course for Alzheimer’s disease (AD) dementia and discordant amyloid-β positron-emission tomography (PET) and cerebrospinal fluid biomarkers. Brain magnetic resonance imaging revealed remarkable atrophy in the hippocampus. However, repeated delayed <sup>18</sup>F-flutemetamol brain amyloid PET images with 1 year-interval revealed no amyloid deposition, whereas her CSF revealed low Aβ42, high total tau and p-tau181. This discordant amyloid-β PET and CSF biomarkers in this early-onset AD dementia might be associated with her low resilience or mixed pathology.

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Principal components of tau positron emission tomography and longitudinal tau accumulation in Alzheimer’s disease

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00685-4 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Hanna Cho ◽

Min Seok Baek ◽

Hye Sun Lee ◽

Jae Hoon Lee ◽

Young Hoon Ryu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Positron Emission Tomography ◽

Distribution Pattern ◽

Principal Components ◽

Brain Magnetic Resonance Imaging ◽

Amyloid Β ◽

Emission Tomography ◽

Longitudinal Changes ◽

Positron Emission

Abstract Background We aimed to investigate the clinical correlates of principal components (PCs) of tau positron emission tomography (PET) and their predictability for longitudinal changes in tau accumulation in Alzheimer’s disease (AD). Methods We enrolled 272 participants who underwent two PET scans [18F-flortaucipir for tau and 18F-florbetaben for amyloid-β (Aβ)], brain magnetic resonance imaging, and neuropsychological tests as baseline assessments. Among them, 187 participants underwent the same follow-up assessments after an average of 2 years. Using Aβ-positive AD dementia-specific PCs obtained from the baseline scans of 56 Aβ-positive patients with AD dementia, we determined the expression of the first two PCs (PC1 and PC2) in all participants. We assessed the correlation of PC expression with baseline clinical characteristics and tau accumulation rates. Moreover, we investigated the predictability of PCs for the longitudinal tau accumulation in training and test sets. Results PC1 corresponded to the tau distribution pattern in AD, while the two PC2 extremes reflected the parietal or temporal predominance of tau distribution. PC1 expression increased with tau burden and decreased with cognitive impairment, while PC2 expression decreased with advanced age and visuospatial and attention function deterioration. The tau accumulation rate was positively correlated with PC1 expression (greater tau burden) and negatively correlated with PC2 expression (temporal predominance). A regression model using both PCs could predict longitudinal changes in the tau burden (intraclass correlation coefficient = 0.775, R2 = 0.456 in test set). Conclusions PC analysis of tau PET could be useful for evaluating disease progression, characterizing the tau distribution pattern, and predicting longitudinal tau accumulation.

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Brain accumulation of amyloid β protein visualized by positron emission tomography and BF-227 in Alzheimer's disease patients with or without diabetes mellitus

Geriatrics and Gerontology International ◽

10.1111/j.1447-0594.2012.00880.x ◽

2012 ◽

Vol 13 (1) ◽

pp. 215-221 ◽

Cited By ~ 15

Author(s):

Naoki Tomita ◽

Katsutoshi Furukawa ◽

Nobuyuki Okamura ◽

Manabu Tashiro ◽

Kaori Une ◽

...

Keyword(s):

Diabetes Mellitus ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Positron Emission Tomography ◽

Amyloid Β ◽

Emission Tomography ◽

Amyloid Β Protein ◽

Positron Emission ◽

Β Protein

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[18 F]flutemetamol amyloid positron emission tomography in preclinical and symptomatic Alzheimer's disease: Specific detection of advanced phases of amyloid-β pathology

Alzheimer s & Dementia ◽

10.1016/j.jalz.2015.05.018 ◽

2015 ◽

Vol 11 (8) ◽

pp. 975-985 ◽

Cited By ~ 75

Author(s):

Dietmar Rudolf Thal ◽

Thomas G. Beach ◽

Michelle Zanette ◽

Kerstin Heurling ◽

Aruna Chakrabarty ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Positron Emission Tomography ◽

Amyloid Β ◽

Emission Tomography ◽

Specific Detection ◽

Amyloid Positron Emission Tomography ◽

Positron Emission ◽

Disease Specific

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Pathogenic PSEN1 Thr119Ile Mutation in Two Korean Patients with Early-Onset Alzheimer’s Disease

Diagnostics ◽

10.3390/diagnostics10060405 ◽

2020 ◽

Vol 10 (6) ◽

pp. 405

Author(s):

Eva Bagyinszky ◽

Hyon Lee ◽

Jung Min Pyun ◽

Jeewon Suh ◽

Min Ju Kang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Positron Emission Tomography ◽

Early Onset ◽

Emission Tomography ◽

Korean Patients ◽

Positron Emission ◽

Mri Scans ◽

Early Onset Alzheimer’S Disease

We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer’s disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magnetic resonance imaging (MRI) scans showed diffuse atrophy in the fronto-parietal regions. In addition, 18F-fludeoxyglucose positron emission tomography (FDG-PET) showed reduced tracer uptake in the parietal and temporal cortices, bilaterally. The second patient developed memory dysfunction at the age of 49, and his mother was also affected. Amyloid positron emission tomography (PET) was positive, but MRI scans did not reveal any atrophy. Targeted NGS and Sanger sequencing identified a heterozygous C to T exchange in PSEN1 exon 5 (c.356C>T), resulting in a p.Thr119Ile mutation. The mutation is located in the conserved HL-I loop, where several Alzheimer’s disease (AD) related mutations have been described. Structure analyses suggested that Thr119Ile mutation may result in a significant change inside conservative loop. Additional in vitro studies are needed to estimate the role of the PSEN1 Thr119Ile in AD disease progression.

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