An 86-year-old man has become progressively unable to live independently for the past 10 years, and he now requires assistance with bathing, dressing, toileting, feeding, and transfers in and out of chairs and bed. On physical examination, he has no motor or sensory deficits. He cannot give the current date or state where he is. Six months later, he suddenly becomes comatose and dies. At autopsy, there is a large superficial left parietal lobe hemorrhage. Histologic examination of the brain shows numerous neocortical neuritic plaques and neurofibrillary tangles. The peripheral cerebral arteries and the core of each plaque stain positively with Congo red. Which of the following mechanisms is most likely responsible for his disease?
An 86-year-old man has become progressively unable to live independently for the past 10 years, and he now requires assistance with bathing, dressing, toileting, feeding, and transfers in and out of chairs and bed. On physical examination, he has no motor or sensory deficits. He cannot give the current date or state where he is. Six months later, he suddenly becomes comatose and dies. At autopsy, there is a large superficial left parietal lobe hemorrhage. Histologic examination of the brain shows numerous neocortical neuritic plaques and neurofibrillary tangles. The peripheral cerebral arteries and the core of each plaque stain positively with Congo red. Which of the following mechanisms is most likely responsible for his disease?
π‘ Explanation
**Core Concept**
The underlying principle in this question is the pathophysiology of a neurodegenerative disorder characterized by the accumulation of abnormal proteins in the brain, leading to neuronal damage and death. This condition is associated with cognitive decline, dementia, and ultimately, death.
**Why the Correct Answer is Right**
The patient's symptoms, including progressive cognitive decline, inability to perform daily activities, and eventually, coma, are indicative of Alzheimer's disease (AD). The presence of numerous neocortical neuritic plaques and neurofibrillary tangles in the brain is a hallmark of AD. The peripheral cerebral arteries and the core of each plaque staining positively with Congo red suggests amyloid angiopathy, a common feature of AD. The accumulation of amyloid-beta (AΞ²) peptides in the brain is a key mechanism in the pathogenesis of AD, leading to neuronal damage and death.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because it refers to a different neurodegenerative disorder, Parkinson's disease, which is characterized by motor symptoms such as tremors, rigidity, and bradykinesia, not cognitive decline.
**Option B:** This option is incorrect because it refers to a type of dementia caused by a vascular event, such as a stroke, leading to cognitive decline. However, the patient's symptoms and autopsy findings do not suggest vascular dementia.
**Option C:** This option is incorrect because it refers to a prion disease, such as Creutzfeldt-Jakob disease, which is characterized by rapid cognitive decline, myoclonus, and eventually, death. However, the patient's symptoms and autopsy findings do not suggest a prion disease.
**Option D:** This option is incorrect because it refers to a type of dementia caused by a metabolic disorder, such as hypothyroidism or vitamin B12 deficiency. However, the patient's symptoms and autopsy findings do not suggest a metabolic disorder.
**Clinical Pearl / High-Yield Fact**
Amyloid angiopathy is a common feature of Alzheimer's disease and can lead to hemorrhagic strokes. This is a high-yield fact for medical students and physicians to recognize the importance of amyloid accumulation in the pathogenesis of AD.
**Correct Answer:** D. Amyloid-beta accumulation.
β Correct Answer: A. Aggregation of Ab peptide
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