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Early-onset Alzheimer's disease Wiki2Web Clarity Challenge

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Study Guide: Early-Onset Alzheimer's Disease: Etiology, Manifestations, and Research Landscape

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Early-Onset Alzheimer's Disease: Etiology, Manifestations, and Research Landscape Study Guide

Core Concepts and Epidemiology of EOAD

Early-onset Alzheimer's disease (EOAD) is typically diagnosed in individuals aged 65 or older.

Answer: False

Explanation: Contrary to the statement, Early-Onset Alzheimer's Disease (EOAD) is characterized by diagnosis typically occurring in individuals younger than 65 years of age.

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Early-onset Alzheimer's disease represents the vast majority of all diagnosed Alzheimer's cases.

Answer: False

Explanation: Early-onset Alzheimer's disease is considered an uncommon form, constituting only approximately 5% to 10% of all diagnosed Alzheimer's disease cases.

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A significant majority, around 60%, of individuals diagnosed with EOAD report a family history of the condition.

Answer: True

Explanation: Epidemiological data indicates that approximately 60% of individuals diagnosed with early-onset Alzheimer's disease have a positive family history, suggesting a genetic predisposition in a substantial proportion of cases.

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All identified cases of early-onset Alzheimer's disease are definitively linked to specific, known genetic mutations.

Answer: False

Explanation: While familial forms are linked to specific mutations, most cases of early-onset Alzheimer's disease share characteristics with the late-onset form and are not definitively attributed to known genetic mutations.

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The typical age range for symptom onset in early-onset Alzheimer's disease is between 30 and 60 years.

Answer: True

Explanation: Early-onset Alzheimer's disease typically manifests symptoms in individuals between the ages of 30 and 60, distinguishing it from the more common late-onset form.

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YOAD is an alternative acronym for Early-Onset Alzheimer's Disease, standing for 'Younger-Onset Alzheimer's Disease'.

Answer: True

Explanation: The acronym YOAD, signifying Younger-Onset Alzheimer's Disease, is indeed used interchangeably with Early-Onset Alzheimer's Disease (EOAD).

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Nonfamilial cases of Alzheimer's disease are commonly referred to as 'familial' AD.

Answer: False

Explanation: Nonfamilial cases of Alzheimer's disease are typically designated as 'sporadic' AD, distinguishing them from cases with a clear genetic inheritance pattern.

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Familial Alzheimer's disease constitutes the majority of early-onset Alzheimer's disease cases.

Answer: False

Explanation: Familial Alzheimer's disease represents a minority, approximately 10% to 15%, of early-onset Alzheimer's disease cases; the majority are sporadic.

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Non-genetic risk factors for early-onset sporadic AD are well-understood and extensively documented.

Answer: False

Explanation: Non-genetic risk factors for early-onset sporadic Alzheimer's disease are not yet well-understood and remain an active area of research.

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What is the defining characteristic of Early-Onset Alzheimer's Disease (EOAD)?

Answer: Diagnosis occurring in individuals before the age of 65.

Explanation: The defining criterion for Early-Onset Alzheimer's Disease (EOAD) is its diagnosis in individuals prior to reaching the age of 65.

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What percentage of all diagnosed Alzheimer's cases are estimated to be early-onset?

Answer: About 5% to 10%

Explanation: Early-onset Alzheimer's disease constitutes a relatively small proportion of all diagnosed cases, estimated to be between 5% and 10%.

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What proportion of individuals with EOAD have a positive family history of the condition?

Answer: Approximately 60%

Explanation: A significant majority, approximately 60%, of individuals diagnosed with early-onset Alzheimer's disease report a familial history of the disease.

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What is the typical age range for the onset of symptoms in early-onset Alzheimer's disease?

Answer: 30 to 60 years

Explanation: The onset of symptoms for early-onset Alzheimer's disease typically occurs between the ages of 30 and 60 years.

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Which acronym is also used to refer to Early-Onset Alzheimer's Disease?

Answer: YOAD

Explanation: YOAD, an abbreviation for Younger-Onset Alzheimer's Disease, is frequently used as an alternative term for Early-Onset Alzheimer's Disease (EOAD).

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Nonfamilial cases of Alzheimer's disease are commonly described using which term?

Answer: Sporadic AD

Explanation: Nonfamilial cases of Alzheimer's disease are typically referred to as 'sporadic AD', indicating the absence of a clear, identifiable genetic inheritance pattern.

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Genetic Basis of Familial EOAD

Familial early-onset Alzheimer's disease is inherited in an autosomal dominant pattern, meaning a mutation in one gene copy is sufficient.

Answer: True

Explanation: Familial early-onset Alzheimer's disease often follows an autosomal dominant inheritance pattern, where a mutation in a single gene copy is sufficient to transmit the condition from parent to offspring.

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Familial Alzheimer's disease is caused by mutations in genes such as PSEN1, PSEN2, and APOE.

Answer: False

Explanation: The primary genetic causes of familial Alzheimer's disease are mutations in the PSEN1, PSEN2, and APP genes. APOE is primarily associated with risk for late-onset Alzheimer's disease, not as a direct cause of familial EOAD.

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The PSEN1 gene is located on chromosome 14 and its link to familial AD was established in 1995.

Answer: True

Explanation: The PSEN1 gene, a significant contributor to familial Alzheimer's disease, is located on chromosome 14 and its association was identified in 1995.

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Over 90 mutations have been identified in the PSEN2 gene linked to familial AD.

Answer: False

Explanation: The source material indicates that over 90 mutations have been identified in the PSEN1 gene, not the PSEN2 gene.

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Mutations in the PSEN2 gene account for a substantial portion, over 10%, of EOFAD cases.

Answer: False

Explanation: Mutations in the PSEN2 gene account for less than 5% of early-onset familial Alzheimer's disease (EOFAD) cases, not over 10%.

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The PSEN2 gene is located on chromosome 1 and was identified by Rudolph Tanzi and Jerry Schellenberg.

Answer: True

Explanation: The PSEN2 gene, implicated in familial Alzheimer's disease, is situated on chromosome 1 and its association was identified by Rudolph Tanzi and Jerry Schellenberg.

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Mutations in the APP gene can cause familial Alzheimer's disease and account for up to 15% of EOFAD cases.

Answer: True

Explanation: Mutations within the Amyloid Precursor Protein (APP) gene are known to cause familial Alzheimer's disease and contribute up to 10% to 15% of EOFAD cases.

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The London mutation (APP V717I) is known to enhance the overall production of Aβ peptides.

Answer: False

Explanation: The London mutation (APP V717I) is associated with altering the ratio of Aβ forms, favoring the more toxic Aβ42, whereas the Swedish mutation enhances the overall production of Aβ peptides.

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The Arctic mutation (APP E693G) is associated with changes in the Aβ peptide structure, leading to increased formation of harmful protofibrils.

Answer: True

Explanation: The Arctic mutation (APP E693G) is known to alter the structure of the Aβ peptide, thereby promoting the formation of toxic protofibrils.

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Familial early-onset Alzheimer's disease is typically inherited in which manner?

Answer: Autosomal dominant

Explanation: Familial early-onset Alzheimer's disease is predominantly inherited in an autosomal dominant pattern, indicating that a mutation in a single gene copy is sufficient to cause the condition.

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Which of the following genes is NOT typically cited as a cause of familial early-onset Alzheimer's disease?

Answer: Apolipoprotein E (APOE)

Explanation: While PSEN1, APP, and PSEN2 are directly implicated as causative genes for familial EOAD, APOE is primarily recognized as a significant risk factor gene for late-onset Alzheimer's disease.

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Which gene mutation is responsible for the largest proportion of early-onset *familial* Alzheimer's disease cases?

Answer: PSEN1

Explanation: Mutations in the Presenilin 1 (PSEN1) gene are the most frequent cause of early-onset familial Alzheimer's disease (EOFAD), accounting for a substantial percentage of cases.

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The PSEN1 gene, linked to familial AD, is located on which chromosome?

Answer: Chromosome 14

Explanation: The PSEN1 gene, critically involved in familial Alzheimer's disease, is located on chromosome 14.

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Which specific APP mutation is cited as enhancing the production of Aβ peptides?

Answer: Swedish Mutation (APP K670M/N671L)

Explanation: The Swedish mutation (APP K670M/N671L) is specifically identified as enhancing the production rate of amyloid-beta (Aβ) peptides.

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The Arctic mutation (APP E693G) primarily affects which aspect of amyloid-beta?

Answer: Its tendency to form harmful protofibrils.

Explanation: The Arctic mutation (APP E693G) influences the structure of amyloid-beta, leading to an increased propensity for forming harmful protofibrils.

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Genetic testing for EOFAD can identify a specific mutation in approximately what percentage of affected families?

Answer: 40% to 80%

Explanation: Genetic testing is capable of identifying a specific causative mutation in approximately 40% to 80% of families affected by early-onset familial Alzheimer's disease (EOFAD).

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Clinical Presentation and Disease Progression

A significant early symptom of EOAD involves difficulty recalling recent events and the names of people.

Answer: True

Explanation: A hallmark early symptom of EOAD is impaired recall of recent events and personal names, often indicative of early cognitive decline.

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As EOAD progresses, individuals typically experience enhanced judgment and improved language fluency.

Answer: False

Explanation: Disease progression in EOAD is associated with declining cognitive functions, including impaired judgment and language disturbances, rather than enhancement.

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In the advanced stages of EOAD, individuals may lose the ability to perform simple daily activities and require constant care.

Answer: True

Explanation: Advanced stages of EOAD are characterized by significant functional decline, including the inability to manage daily activities and the need for continuous care.

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Later stages of EOAD can involve symptoms such as hallucinations, seizures, and loss of bladder control.

Answer: True

Explanation: Advanced stages of EOAD may present with complex neurological symptoms including hallucinations, seizures, and loss of bladder and bowel control.

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Brain atrophy refers to the progressive shrinking of brain volume as neurons are damaged and die.

Answer: True

Explanation: Brain atrophy is defined as the progressive reduction in brain volume resulting from neuronal damage and death, a characteristic pathological feature in neurodegenerative diseases like Alzheimer's.

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What is a primary early symptom related to memory in EOAD?

Answer: Unusual memory loss concerning recent events and names.

Explanation: A significant early indicator of EOAD is pronounced memory impairment, specifically difficulty recalling recent events and the names of individuals.

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As EOAD progresses, which cognitive or behavioral change is likely to occur?

Answer: Difficulty with complex tasks such as driving.

Explanation: As EOAD advances, individuals often experience a decline in executive functions, leading to difficulties with complex tasks like driving, alongside other cognitive impairments.

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What is a characteristic symptom of the later stages of EOAD?

Answer: Loss of ability to perform simple daily activities like grooming.

Explanation: Later stages of EOAD are marked by severe cognitive and functional deficits, including the loss of capacity to perform basic activities of daily living such as personal grooming.

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What does the term 'brain atrophy' refer to in the context of Alzheimer's disease?

Answer: The progressive shrinking of brain volume due to neuronal damage.

Explanation: Brain atrophy signifies the progressive reduction in brain volume, a consequence of neuronal loss and damage characteristic of neurodegenerative conditions like Alzheimer's disease.

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Diagnosis, Research, and Medical Classification

The diagnosis and management of Early-Onset Alzheimer's Disease primarily fall under the specialty of Cardiology.

Answer: False

Explanation: The diagnosis and management of Early-Onset Alzheimer's Disease are primarily within the domain of Neurology, not Cardiology.

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Histologically, familial Alzheimer's disease is characterized by the absence of amyloid deposits.

Answer: False

Explanation: Histological examination of familial Alzheimer's disease brain tissue reveals the presence of amyloid deposits, which form plaques and neurofibrillary tangles, similar to other forms of the disease.

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Beta-amyloid (Aβ) fragments aggregate sequentially into oligomers, fibrils, and ultimately form amyloid plaques in the brain.

Answer: True

Explanation: The pathological cascade in Alzheimer's disease involves the sequential aggregation of beta-amyloid fragments into progressively larger structures, culminating in the formation of amyloid plaques.

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The gamma-secretase complex, crucial for APP processing, includes APP itself as a core enzymatic component.

Answer: False

Explanation: The gamma-secretase complex's core enzymatic components are presenilins 1 and 2, not APP itself.

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Genetic testing for EOAD is available for both symptomatic individuals and their asymptomatic relatives within affected families.

Answer: True

Explanation: Genetic testing for early-onset familial Alzheimer's disease is a clinical option for both individuals exhibiting symptoms and their unaffected relatives within affected lineages.

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Cognitive rehabilitation has shown potential benefits in supporting daily functioning and independence for individuals with EOAD.

Answer: True

Explanation: Evidence suggests that cognitive rehabilitation interventions can positively impact daily functioning and promote independence among individuals diagnosed with EOAD.

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Glial cells, such as astrocytes and microglia, play a role in the neuroinflammatory processes associated with Alzheimer's disease.

Answer: True

Explanation: Glial cells, including astrocytes and microglia, are integral components of the neuroinflammatory response observed in Alzheimer's disease pathology.

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The ICD-10 code F00.0 is used for early-onset Alzheimer's disease.

Answer: False

Explanation: The ICD-10 code G30.0 specifically designates early-onset Alzheimer's disease, while F00.0 is used for dementia in Alzheimer's disease with early onset.

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Early-onset familial Alzheimer's disease (EOFAD) is considered a valuable research model primarily because of its high prevalence compared to other forms.

Answer: False

Explanation: EOFAD is valued as a research model not due to high prevalence, but because its known genetic mutations provide a clear basis for studying disease mechanisms, despite its overall rarity.

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What are the core enzymatic components of the gamma-secretase complex involved in APP processing?

Answer: Presenilins 1 and 2, Nicastrin, Aph1, and PEN-2

Explanation: The gamma-secretase complex, essential for cleaving APP, comprises presenilins 1 and 2 as its catalytic subunits, along with nicastrin, Aph1, and PEN-2.

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What role do glial cells play in the neurobiology of Alzheimer's disease?

Answer: They are integral to neuroinflammatory processes activated by beta-amyloid.

Explanation: Glial cells, such as astrocytes and microglia, are activated by pathological hallmarks like beta-amyloid plaques and contribute significantly to the neuroinflammatory processes underlying Alzheimer's disease.

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What is the ICD-10 classification code for early-onset Alzheimer's disease?

Answer: G30.0

Explanation: The International Classification of Diseases, 10th Revision (ICD-10) code G30.0 is designated for early-onset Alzheimer's disease.

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Why is early-onset familial Alzheimer's disease (EOFAD) considered a valuable research model despite its rarity?

Answer: Its known genetic mutations provide a clear basis for studying disease mechanisms.

Explanation: EOFAD serves as a crucial research model because the identified genetic mutations offer a direct pathway to investigate the underlying molecular mechanisms of Alzheimer's disease pathogenesis.

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What is the Medical Subject Headings (MeSH) identifier for Alzheimer's disease?

Answer: D000544

Explanation: The Medical Subject Headings (MeSH) identifier for Alzheimer's disease is D000544.

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Societal Impact and Awareness

The novel and film 'Still Alice' primarily focuses on the challenges of late-onset Alzheimer's disease.

Answer: False

Explanation: The narrative of 'Still Alice' centers on the experiences of an individual diagnosed with early-onset Alzheimer's disease, significantly contributing to public awareness of this form.

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The novel and film 'Still Alice' is highlighted for its role in:

Answer: Raising public awareness about early-onset Alzheimer's disease.

Explanation: 'Still Alice' has been instrumental in increasing public understanding and awareness regarding the challenges posed by early-onset Alzheimer's disease.

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The early onset of EOAD can have a profound impact on a patient's:

Answer: Career, financial independence, and family dynamics.

Explanation: The premature onset of EOAD significantly disrupts patients' professional lives, financial stability, and familial relationships, often during their most productive years.

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The documentary film 'Spirit Unforgettable' chronicles the farewell tour of which musician diagnosed with EOAD?

Answer: John Mann

Explanation: 'Spirit Unforgettable' documents the final tour of musician John Mann, who was diagnosed with early-onset Alzheimer's disease.

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What does the Indian film 'Thanmathra' explore?

Answer: The impact of early-onset Alzheimer's disease on a father-son relationship.

Explanation: The Indian film 'Thanmathra' provides a poignant exploration of how early-onset Alzheimer's disease affects a father and his relationship with his son.

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What perspective is suggested regarding the distinction between early-onset Alzheimer's disease and normal aging?

Answer: Conceptualizations should avoid a rigid binary distinction to avoid minimizing challenges faced by older individuals.

Explanation: It is advocated that conceptual frameworks should refrain from establishing a strict binary distinction between EOAD and normal aging, thereby preventing the inadvertent minimization of challenges faced by older individuals with dementia.

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