Name: quantitative 3d in silico modeling (q3dism) of cerebral amyloid-beta phagocytosis in rodent models of alzheimer's disease
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M-V.G-S. is supported by a BrightFocus Foundation Alzheimer's Disease Research Fellowship Award (A2015309F) and an Alzheimer's Association, California Southland Chapter Young Investigator Award. T.M.W. is supported by an ARCS Foundation and John Douglas French Alzheimer's Foundation Maggie McKnight Russell-JDFAF Memorial Postdoctoral Fellowship. This work was supported by the National Institute on Neurologic Disorders and Stroke (1R01NS076794-01, to T.T.), an Alzheimer's Association Zenith Fellows Award (ZEN-10-174633, to T.T.), and an American Federation of Aging Research/Ellison Medical Foundation Julie Martin Mid-Career Award in Aging Research (M11472, to T.T.). We are grateful for startup funds from the Zilkha Neurogenetic Institute, which helped to make this work possible. &#8195;

Araştırma etiği Beyanı: Burada detaylı hayvanları da içeren tüm deneylerde Southern California Kurumsal Hayvan Bakımı ve Kullanımı Komitesi (IACUC) Üniversitesi tarafından onaylanmış ve Laboratuar Değerlendirme ve Akreditasyon Derneği Ulusal Sağlık kılavuzların Enstitüleri ve önerileri ile tam uyum içinde yapıldı hayvan Bakımı Uluslararası. 1. Kemirgen Beyin İzolasyon ve immün için hazırlık 1.GÜN: <ol><li> yaşlı TgF344-AD sıçan yerleştirin (14 a...

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Biz mononükleer fagositler tarafından in vivo Aβ fagositoz gerçek 3D kantitatif için bu raporda tarif protokol spesifik hücresel ve hücre içi bölmelerin etiketleme yanı sıra Aβ mevduat dayanmaktadır. Özellikle, Iba1 (İyonize kalsiyum Adaptör molekülü 1. Bağlayıcı), hücre aktivasyonunun 18, 19 üzerine doğrudan membran kırışması oluşur ve fagositoz dahil olan bir proteinin, serebral mononükleer fagositler leke için kullanın. Iba1 + hücre...

Alzheimer hastalığı (AD), en sık yaşa bağlı dementia, 1 &quot;senil&quot; β-amiloid plaklarının kronik düşük seviyeli nöroenflamasyonun, tauopathy, nöronal kayıp, ve bilişsel bozukluk 2 gibi serebral amiloid-β (Aβ) birikimi ile karakterize edilir . AD hasta beyinlerinde, Nöroenflamasyon astrositler ve mononükleer fagositler reaktif tarafından tahsis edilir çevreleyen Aβ mevduat 3 (onların periferik kökenli belirsizdir vs merkezi olmasına rağmen, mikroglia olarak anılacaktır). MSS doğuştan gelen bağışıklık gözcüler olarak, mikroglia merkezi beyin Aβ temizlemek için konumlandırılmış. Bununla birlikte, Aβ plaklara mikrogliyal alımları, eğer varsa, çok az Aβ fagositoz 4,5 eşlik eder. Bir hipotez mikroglia Aβ küçük meclisleri phagocytozing başlangıçta nöro-koruyucu olmasıdır. Ancak, sonunda bu hücrelerin ezici Aβ yükü ve / veya yaşa bağlı fonksiyonel d gibi nörotoksik haleecline, nörotoksisite ve bilişsel gerileme 6 katkıda işlevsiz bir proinflamatuar fenotip içine mikroglia kışkırtır. Son genom Derneği Çalışmaları (GWAS) fagositoz 8-11 modüle çekirdek doğuştan gelen bağışıklık yolların 7 ait AD risk allelleri bir küme belirledik. Sonuç olarak, serebral amiloid birikimi bağışıklık tepkisi AD etiyolojisinin daha iyi anlaşılması açısından ve yeni tedavi yaklaşımları 12-14 geliştirmek için hem ilgi önemli bir alan haline gelmiştir. Bununla birlikte, in vivo koşullarında Aβ fagositoz değerlendirmek için yöntem için önemli bir ihtiyaç vardır. Bu karşılanmamış gereksinimi karşılamak için, Alzheimer-benzeri hastalığının kemirgen modellerinde mononükleer fagositler tarafından serebral Aβ fagositoz gerçek 3D kantitatif sağlamak için silikon modelleme (q3DISM) &#39;de niceliksel 3D geliştirdik. Onlar, hayvan modelleri hastalığı recapitulate ölçüde sadece sınırlıAD pathoetiology anlaşılması için ve deneysel terapötik maddelerin değerlendirilmesi için çok değerli kanıtlanmıştır. Presenilin (PS) ve Amiloid Prekürsör Protein (APP) genlerindeki mutasyonlar, bağımsız bir otozomal baskın AH nedeni olduğu gerçeği nedeniyle, bu mutan transgenler yoğun transjenik rodent modelleri oluşturmak için kullanılmıştır. Transgenik APP / PS1 fareler aynı anda &quot;İsveç&quot; mutant insan APP (APPswe) ve hızlandırılmış serebral amiloidoz ve nöro 15,16 ile mevcut Δ ekson 9 mutant insan presenilin 1 (PS1ΔE9) coexpressing. Ayrıca, biz (bir Fischer 344 arka plan üzerinde çizgi TgF344-AD) APP swe ve PS1ΔE9 yapıları ile birlikte enjekte bi-transgenik fareler yarattı. Serebral amiloidoz transgenik fare modellerinde farklı olarak, TgF344-AD sıçan tauopathy, nöronların apoptotik kaybı ve davranış bozukluğu 17 önce gelen serebral amiloid geliştirme. Bu yazıda imm için bir protokol açıklarAPP / PS1 fareler ve TgF344-AD sıçan ve büyük z boyutlu eş odaklı görüntü edinme beyin bölümlerinde mikroglia fagolizozomları ve Aβ mevduat unostaining. Siliko üretimi ve mikroglial fagolizozomları içine Aβ alımının kantitatif izin konfokal veri setlerinden gerçek 3D rekonstrüksiyon analizinde Biz ayrıntı. Daha genel olarak, burada ayrıntılı metodoloji in vivo fagositoz hemen hemen herhangi bir şekilde ölçmek için kullanılabilir.

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			<td height="40" style="height:40px;width:384px;">Isoflurane</td>
			<td style="width:152px;">Abbott</td>
			<td style="width:127px;">NDC 0044-5260-05</td>
			<td style="width:249px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Dissecting scissors</td>
			<td style="width:152px;">VWR</td>
			<td style="width:127px;">82027-582</td>
			<td></td>
		</tr>
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			<td height="20" style="height:20px;width:384px;">Dissecting scissors Blunt tip</td>
			<td style="width:152px;">VWR</td>
			<td style="width:127px;">82027-588</td>
			<td></td>
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		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Tweezers</td>
			<td style="width:152px;">VWR</td>
			<td>94024-408</td>
			<td></td>
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			<td height="20" style="height:20px;width:384px;">23G needle</td>
			<td style="width:152px;">VWR</td>
			<td>BD305145</td>
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			<td height="20" style="height:20px;width:384px;">peristaltic pump FH10</td>
			<td style="width:152px;">Thermo Scientific</td>
			<td>72-310-010</td>
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			<td height="20" style="height:20px;width:384px;">PBS 10X</td>
			<td style="width:152px;">Bioland Scientific</td>
			<td style="width:127px;">PBS01-02</td>
			<td>Working concentration 1X</td>
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			<td height="20" style="height:20px;width:384px;">Adult Mouse Brain Matrix, Coronal slices, Stainless Steel 1mm&#160;</td>
			<td style="width:152px;">Kent Scientific</td>
			<td>RBMS-200C</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Adult Rat Brain Matrix, Coronal slices, Stainless Steel 1mm&#160;</td>
			<td style="width:152px;">Kent Scientific</td>
			<td>RBMS-305C&#160;</td>
			<td></td>
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			<td height="20" style="height:20px;width:384px;">32% Paraformaldehyde aqueous solution</td>
			<td style="width:152px;">EMS</td>
			<td style="width:127px;">15714-S</td>
			<td>Caution: Toxic. Working concentration 4% in PBS</td>
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			<td height="20" style="height:20px;width:384px;">Ethanol</td>
			<td style="width:152px;">VWR</td>
			<td>89125-188</td>
			<td>Various concentrations, see protocol</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Tissue-Tek Uni-cassettes Sakura</td>
			<td style="width:152px;">VWR</td>
			<td>25608-774</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Embedding and Infiltration Paraffin</td>
			<td style="width:152px;">VWR</td>
			<td>15147-839</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Microtome Leica RM2125</td>
			<td style="width:152px;">Leica Biosystems</td>
			<td style="width:127px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Disposable Microtome Blades&#160;</td>
			<td style="width:152px;">VWR</td>
			<td style="width:127px;">25608-964</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Water bath Leica HI 1210</td>
			<td style="width:152px;">Leica Biosystems</td>
			<td style="width:127px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Micro slide Superfrost plus</td>
			<td style="width:152px;">VWR</td>
			<td style="width:127px;">48311-703</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Xylene</td>
			<td style="width:152px;">Sigma-Aldrich</td>
			<td style="width:127px;">534056-4X4L</td>
			<td style="width:249px;">Caution: Toxic&#160;</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Target Retrieval Solution 10X</td>
			<td style="width:152px;">DAKO</td>
			<td style="width:127px;">S1699</td>
			<td>Working concentration 1X</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">KimWipes</td>
			<td style="width:152px;">VWR</td>
			<td>21905-026</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Hydrophobic PAP pen</td>
			<td style="width:152px;">VWR</td>
			<td style="width:127px;">95025-252</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Triton X-100</td>
			<td style="width:152px;">VWR</td>
			<td style="width:127px;">97062-208</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Normal Donkey Serum</td>
			<td style="width:152px;">Jackson Immuno</td>
			<td style="width:127px;">017-000-121</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Coverslips</td>
			<td style="width:152px;">VWR</td>
			<td style="width:127px;">48393081</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Prolong Gold antifade reagent with DAPI</td>
			<td style="width:152px;">Life Technologies</td>
			<td style="width:127px;">P36935</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Glass Slide Rack</td>
			<td style="width:152px;">VWR</td>
			<td style="width:127px;">100492-942</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Iba1 antibody (polyclonal, rabbit)</td>
			<td style="width:152px;">Wako</td>
			<td style="width:127px;">019-19741&#160;</td>
			<td>Working concentration 1:200</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Iba1 antibody (polyclonal, goat)</td>
			<td style="width:152px;">LifeSpan Bioscience</td>
			<td style="width:127px;">LS-B2645</td>
			<td>Working concentration 1:200</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">rat CD68 [KP1] antibody (monoclonal, mouse)</td>
			<td style="width:152px;">Abcam</td>
			<td style="width:127px;">ab955</td>
			<td>Working concentration 1:200</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">mouse CD68 [FA-11] antibody (monoclonal, rat)</td>
			<td style="width:152px;">Abcam</td>
			<td style="width:127px;">ab53444</td>
			<td>Working concentration 1:200</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">mouse CD107a (LAMP1) antibody (monoclonal, rat)</td>
			<td style="width:152px;">Affymetrix</td>
			<td style="width:127px;">14-1071</td>
			<td>Working concentration 1:100</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Beta-Amyloid, 17-24 (4G8) antibody (monoclonal, mouse)</td>
			<td style="width:152px;">Covance</td>
			<td style="width:127px;">SIG-39220</td>
			<td>Working concentration 1:200</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Beta-Amyloid, 1-16 (6E10) antibody (monoclonal, mouse)</td>
			<td style="width:152px;">Covance</td>
			<td style="width:127px;">SIG-39320</td>
			<td>Working concentration 1:200</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">OC antibody (polyclonal, rabbit)</td>
			<td colspan="2">Gifted by D. H. Cribbs and C. G. Glabe (UC Irvine)</td>
			<td>Working concentration 1:200</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Alexa Fluor 488&#160; mouse secondary antibody</td>
			<td style="width:152px;">Invitrogen</td>
			<td style="width:127px;">A-11001</td>
			<td>Working concentration 1:1000</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Alexa Fluor 488&#160; rat secondary antibody</td>
			<td style="width:152px;">Invitrogen</td>
			<td>A-11006</td>
			<td>Working concentration 1:1000</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Alexa Fluor 594 rabbit secondary antibody</td>
			<td style="width:152px;">Invitrogen</td>
			<td>A-11037</td>
			<td>Working concentration 1:1000</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Alexa Fluor 594 goat secondary antibody</td>
			<td style="width:152px;">Invitrogen</td>
			<td>A-11080</td>
			<td>Working concentration 1:1000</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Alexa Fluor 647 mouse secondary antibody</td>
			<td style="width:152px;">Invitrogen</td>
			<td>A-21235</td>
			<td>Working concentration 1:1000</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Alexa Fluor 647 rabbit secondary antibody</td>
			<td style="width:152px;">Invitrogen</td>
			<td>A-21443</td>
			<td>Working concentration 1:1000</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Immersion oil</td>
			<td style="width:152px;">Nikon&#160;</td>
			<td style="width:127px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">A1 Confocal microscope</td>
			<td style="width:152px;">Nikon&#160;</td>
			<td style="width:127px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">NIS Elements Advanced Research software</td>
			<td style="width:152px;">Nikon&#160;</td>
			<td style="width:127px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;">Imaris:Bitplane software version 7.6</td>
			<td style="width:152px;">Bitplane</td>
			<td style="width:127px;"></td>
			<td>&#34;coloc&#34; and &#34;supass&#34; modules are used.&#160;Alternatively, the open-source freeware&#160;ImageJ can be used for colocalization&#160;analysis of confocal z-stacks datasets.</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td style="width:152px;"></td>
			<td style="width:127px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;"></td>
			<td style="width:152px;"></td>
			<td style="width:127px;"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:384px;"></td>
			<td style="width:152px;"></td>
			<td style="width:127px;"></td>
			<td></td>
		</tr>
	</tbody>
</table>

quantitative 3d in silico modeling (q3dism) of cerebral amyloid-beta phagocytosis in rodent models of alzheimer's disease

Nöroenflamasyon şimdi nörodejeneratif hastalık önemli bir etyolojik faktör olarak kabul edilmektedir. Mononükleer fagositler fagositoz ve enkaz ve döküntü temizlenmesi için sorumlu doğuştan gelen bağışıklık hücreleridir. Bu hücreler, çevreden süzücü mikroglia olarak bilinen merkezi sinir sistemi yerleşik makrofajlar ve mononükleer fagositler bulunmaktadır. Işık mikroskobu genellikle kemirgen ya da insan beyni örneklerinde fagositoz görselleştirmek için kullanılır olmuştur. Ancak, kalitatif yöntemler in vivo fagositoz kesin delil değil. Burada, silikon modelleme (q3DISM), kemirgen Alzheimer hastalığı (AD), bir model mononükleer fagositler tarafından amiloid-β (Aβ) fagositoz gerçek 3D niceliğinin belirlenmesine olanak sağlam bir yöntem kantitatif 3D açıklar. yöntem, floresan Aβ kemirgen beyin bölümlerinde fagolizozomları içinde kapsüllenmiş visualising içerir. Büyük z-boyutlu konfokal veri setleri daha sonra 3D A &amp; miktarının belirlenmesi için yeniden inşa edilir# 946; mekansal phagolysosome içinde kolokalize. Bu fare ve sıçan beynine q3DISM başarılı bir uygulama göstermektedir, ancak bu yöntem herhangi bir dokuda hemen hemen herhangi bir fagositik etkinlik için uzatılabilir.

Q3DISM yukarıda ayrıntıları için çok-aşamalı bir yöntem kullanarak, APP / PS1 farelerde (Şekil 1) ve TgF344 AD farelerde (Şekil 2) beyinlerinde monosit fagolizozomları halinde Aβ alımını ölçmek mümkündür. Bu nedenle, q3DISM yöntemi AD fare ve sıçan modellerinde mononükleer fagositler analizi sağladı. İlginç bir şekilde, CD68 + fagolizozomları tarafından işgal edilen hacim miktarı hem APP / PS1 fareleri <strong...

Watch this Scientific Journal Video about Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease at JoVE.com

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease

Alzheimer hastalığı, kemirgen modellerinde mononükleer fagositler tarafından serebral amiloid-β (Aβ) fagositoz silikon modelleme (q3DISM) nicel 3D için bir yöntem geliştirdi. Bu yöntem, in vivo olarak hemen her fagositik olayın kantitatif için genelleştirilebilir.

kantitatif 3D<em&gt; Siliko</emAlzheimer Hastalığının Kemirgen Modelleri Serebral Amiloid-beta Fagositoz&gt; Modelleme (q3DISM)

Neuroinflammation is now recognized as a major etiological factor in neurodegenerative disease. Mononuclear phagocytes are innate immune cells responsible ...

Research

JoVE Journal

Medicine

Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease

Examining the Characteristics of Episodic Memory using Event-related Potentials in Patients with Alzheimer's Disease

Alzheimer hastalığı olan hastalarda olaya ilişkin potansiyeller kullanarak Episodik Bellek Özellikleri incelenmesi

Our laboratory uses event-related EEG potentials (ERPs) to understand and support behavioral investigations of episodic memory in patients with amnestic ...

Quantitative Analysis of Chromatin Proteomes in Disease

Hastalığında Kromatin Proteomlar Kantitatif Analiz

In the nucleus reside the proteomes whose functions are most intimately linked with gene regulation. Adult mammalian cardiomyocyte nuclei are unique due ...

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease

Parkinson Hastalığında Maskeyi Düşürme Duyarlılık Mekanizmalarına Gen-Çevre Etkileşim Modelleri

Lipoxygenase (LOX) activity has been implicated in neurodegenerative disorders such as Alzheimer&#39;s disease, but its effects in Parkinson&#39;s disease ...

Modeling Stroke in Mice: Permanent Coagulation of the Distal Middle Cerebral Artery

Farelerde Modelleme İnme: Distal Orta Serebral Arter Daimi Pıhtılaşma

Stroke is the third most common cause of death and a main cause of acquired adult disability in developed countries. Only very limited therapeutical ...

Multi-electrode Array Recordings of Human Epileptic Postoperative Cortical Tissue

İnsan Epileptik Ameliyat sonrası Kortikal Doku Çok elektrot Dizi Kayıtlar

Epilepsy, affecting about 1% of the population, comprises a group of neurological disorders characterized by the periodic occurrence of seizures, which ...

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Için Polikistik Böbrek Hastalığında Küçük Kemirgen modelleri Ultra yüksek Saha MRI Kullanımı<em&gt; In Vivo</em&gt; Fenotiplendirme ve İlaç İzleme

Several in vivo pre-clinical studies in Polycystic Kidney Disease (PKD) utilize orthologous rodent models to identify and study the genetic and molecular ...

Ex Vivo Intestinal Sacs to Assess Mucosal Permeability in Models of Gastrointestinal Disease

Ex Vivo Intestinal Sacs to Assess Mucosal Permeability in Models of Gastrointestinal Disease

Ex Vivo Bağırsak Sacs Gastrointestinal Hastalık Modelleri mukozal geçirgenliği Değerlendirmek için

The epithelial barrier is the first innate defense of the gastrointestinal tract and selectively regulates transport from the lumen to the underlying ...

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Pulmoner Hipertansiyon Kemirgen Modeller Hemodinamik Karakterizasyonu

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle ...

Neurodegeneration in an Animal Model of Chronic Amyloid-beta Oligomer Infusion Is Counteracted by Antibody Treatment Infused with Osmotic Pumps

Kronik Amiloid beta Oligomer İnfüzyon bir hayvan Modelinde Nörodejenerasyon Osmotik Pompalar ile Antikor Tedavisi infüzyon ile giderilir

Decline in hippocampal-dependent explicit memory (memory for facts and events) is one of the earliest clinical symptom of Alzheimer&#39;s disease (AD). It ...

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment

Granger Nedensellik analizi yönlendirilmiş fonksiyonel bağlantı hafif kognitif bozukluk ve Alzheimer hastalığı uygulanması

Impaired functional connectivity in the Default Mode Network (DMN) may be involved in the progression of Alzheimer&#39;s Disease (AD). The Posterior ...