Publication: Alzheimer Hastalığı ve Demans
Abstract
Demans, akut bilinç bozukluğu ya da deliryum olmaksızın sant- ral sinir sisteminin hasarına bağlı gelişen, hastanın günlük yaşamını et- kileyen, ilerleyici, en az iki kognitif alanda yıkım ile seyreden semptomların klinik bütünlüğü durumunda konulan bir tanıdır. Alz- heimer hastalığı (AH) ise orta ve geç yaş popülasyonda ortaya çıkan, hafızayı ve düşünme becerileri gibi en basit işleri yapma yeteneğini ya- vaşça yok eden, geri dönüşü olmayan, ilerleyen bir beyin hastalığı- dır. Türkiye’de 65 yaş öncesi AH 30.000-40.000 kişide görülürken, 65 yaş üstünde toplumun %5’ini etkilemekte, 85 yaş üstü popülas- yonun ise %30-50’sinde görülmektedir. Hastalık, klinik olarak bel- lek, konuşma, yüksek serebral işlevler ve görsel-uzaysal beceriler gibi birden çok sistemi etkileyen, bilişsel işlevlerde ilerleyici kayıp ile seyreden, nörolojik açıdan sinaps ve nöron kaybı, gliozis, ami- loid plak ve nörofibriler yumak oluşumları ile karakterizedir. Gene- tik, biyokimyasal ve nöropatolojik veriler, Aβ agregasyonunun AH patogenezinde önemli rol oynadığını göstermektedir. Normal bir nö- ronal membran proteini olan APP’nin kesilmesi sonucu amiloid beta (Aβ) 40/42 olarak adlandırılan ekstraselüler fragman oluşur. Bu nö- rotoksik fragmanlar sıklıkla bir araya toplanır; Aβ 40/42 oligomeri- zasyonu plak oluşumu ile sonuçlanır. Normal fizyolojik koşullar altında glutamat N-metil D-aspartat (NMDA) reseptörlerini uyara- rak kalsiyum iyonlarının postsinaptik aralıktan nöronun içine akma- sını sağlar. Nörona iletilen kalsiyum iyonları beyinde öğrenme, hafıza gibi yüksek düzey işlerin devamını sağlamaktadır. AH’li bi- reylerde biriken Aβ 40/42 plaklar, glutamat NMDA reseptörleri ile aşırı Ca+2 üretimini tetikler. Aşırı üretilen Ca+2 nitrik oksit seviye- sini artırır, mitakondriyal etkinliği engeller ve hücre içi ATP sevi- yesinin tükenmesine neden olarak nöronda enerji kaybına, nöronal disfonksiyona ve hücre ölümüne neden olur
Dementia is a diagnosis of clinical integrity of symp- toms associated with destruction of at least two progressive cognitive areas that affect the daily life of the patient, resulting from damage to the central nervous system without acute impairment or delirium. Alzheimer's disease (AD) is an irreversible, progressive brain disease that slowly eradicates the ability to perform simple tasks such as memory and thinking skills in the middle and late age population. AH 30,000-40,000 before the age of 65 in Turkey affects 5% of the pop- ulation over the age of 65 seen in person, while the population over age 85 is seen in 30-50%. Disease clinically memory, speech, higher cerebral functions and visual. It is characterized by neurological synapse and loss of neurons, gliosis, amyloid plaque and neurofibril- lary tangles, affecting multiple systems such as spatial skills, pro- gressive loss of cognitive functions. Genetic, biochemical and neuropathological data suggest that Aβ aggregation plays an impor- tant role in the pathogenesis of AD. The cutting of APP, a normal neuronal membrane protein, results in an extracellular fragment called amyloid beta (Aβ) 40/42. These neurotoxic fragments are often pooled together; oligomerization of Aβ 40/42 results in plaque for- mation. Under normal physiological conditions, glutamate N-methyl D-aspartate (NMDA) stimulates its receptors to allow calcium ions to flow through the postsynaptic space into the neuron. Calcium ions transmitted to the neuron provide the continuation of high level tasks such as learning and memory in the brain. Accumulated Aβ 40/42 plaques in patients with Alzheimer's disease trigger excess Ca+2 pro- duction by glutamate NMDA receptors. Over-produced Ca+2 increases nitric oxide levels, inhibits mitochondrial activity, and leads to de- pletion of intracellular ATP levels, leading to energy loss, neuronal dysfunction, and cell death.
Dementia is a diagnosis of clinical integrity of symp- toms associated with destruction of at least two progressive cognitive areas that affect the daily life of the patient, resulting from damage to the central nervous system without acute impairment or delirium. Alzheimer's disease (AD) is an irreversible, progressive brain disease that slowly eradicates the ability to perform simple tasks such as memory and thinking skills in the middle and late age population. AH 30,000-40,000 before the age of 65 in Turkey affects 5% of the pop- ulation over the age of 65 seen in person, while the population over age 85 is seen in 30-50%. Disease clinically memory, speech, higher cerebral functions and visual. It is characterized by neurological synapse and loss of neurons, gliosis, amyloid plaque and neurofibril- lary tangles, affecting multiple systems such as spatial skills, pro- gressive loss of cognitive functions. Genetic, biochemical and neuropathological data suggest that Aβ aggregation plays an impor- tant role in the pathogenesis of AD. The cutting of APP, a normal neuronal membrane protein, results in an extracellular fragment called amyloid beta (Aβ) 40/42. These neurotoxic fragments are often pooled together; oligomerization of Aβ 40/42 results in plaque for- mation. Under normal physiological conditions, glutamate N-methyl D-aspartate (NMDA) stimulates its receptors to allow calcium ions to flow through the postsynaptic space into the neuron. Calcium ions transmitted to the neuron provide the continuation of high level tasks such as learning and memory in the brain. Accumulated Aβ 40/42 plaques in patients with Alzheimer's disease trigger excess Ca+2 pro- duction by glutamate NMDA receptors. Over-produced Ca+2 increases nitric oxide levels, inhibits mitochondrial activity, and leads to de- pletion of intracellular ATP levels, leading to energy loss, neuronal dysfunction, and cell death.