Amyloid-related imaging abnormalities

ARIA-E refers to cerebral edema, involving the breakdown of the tight endothelial junctions of the blood-brain barrier and subsequent accumulation of fluid.{{Cite web|url=http://www.alzforum.org/news/conference-coverage/paris-renamed-aria-vasogenic-edema-common-anti-amyloid-therapy|title=Paris: Renamed ARIA, Vasogenic Edema Common to Anti-Amyloid Therapy {{!}} ALZFORUM|website=www.alzforum.org|access-date=2016-12-11}} In a double-blind trial of the humanised monoclonal antibody solanezumab (n = 2042), sixteen patients (11 taking the drug, 5 taking a placebo), or 0.78% developed ARIA-E. A further 7 patients developed ARIA-E during an open-label extension of the trial.{{Cite journal|last1=Carlson|first1=Christopher|last2=Siemers|first2=Eric|last3=Hake|first3=Ann|last4=Case|first4=Michael|last5=Hayduk|first5=Roza|last6=Suhy|first6=Joyce|last7=Oh|first7=Joonmi|last8=Barakos|first8=Jerome|date=2016-03-02|title=Amyloid-related imaging abnormalities from trials of solanezumab for Alzheimer's disease|journal=Alzheimer's & Dementia |volume=2|pages=75–85|doi=10.1016/j.dadm.2016.02.004|issn=2352-8729|pmc=4879647|pmid=27239538}}

The effect of ARIA-E depends on the severity and location of the edema. Symptoms may include headache, changes in mental state, confusion, vomiting, nausea, tremor and gait disturbances.

ARIA-H refers to cerebral microhaemorrhages (mH), small haemorrhages on the brain,{{Cite web|url=https://radiopaedia.org/articles/cerebral-microhaemorrhage|title=Cerebral microhaemorrhage {{!}} Radiology Reference Article {{!}} Radiopaedia.org|last=Gaillard|first=Frank|website=radiopaedia.org|access-date=2016-12-11}} often accompanied by hemosiderosis. mH are usually seen as small, round and low intensity lesions and are small haemosiderin deposits. Some studies define mH as being less than or equal to 10mm, while others define the cut-off as ≤ 5mm. The prevalence of mH in healthy elderly people is approximately 6%, but this value increases to between 50% and 80% in elderly people with cerebrovascular disease.{{Cite journal|last=Fiehler|first=Jens|date=2006-08-01|title=Cerebral microbleeds: old leaks and new haemorrhages|journal=International Journal of Stroke|language=en|volume=1|issue=3|pages=122–130|doi=10.1111/j.1747-4949.2006.00042.x|pmid=18706032|s2cid=11780084|issn=1747-4949}}

File:Amyloid-related imaging abnormalities 01.png)
Middle: ARIA-H with multiple microbleeds (T2* weighted)
Right: ARIA-H with superficial siderosis (T2* weighted)|400x400px]]

Two non-exclusive mechanisms have been postulated. Firstly, in the context of aging and neurodegeneration, the integrity of the blood-brain barrier (BBB) can become compromised, resulting in increased permeability. Notably, amyloid plaques have been hypothesized to counteract this BBB leakage.{{cite journal |last1=Atwood |first1=Craig S. |last2=Bowen |first2=Richard L. |last3=Smith |first3=Mark A. |last4=Perry |first4=George |title=Cerebrovascular requirement for sealant, anti-coagulant and remodeling molecules that allow for the maintenance of vascular integrity and blood supply |journal=Brain Research Reviews |date=September 2003 |volume=43 |issue=1 |pages=164–178 |doi=10.1016/S0165-0173(03)00206-6}} However, upon the administration of antibodies, these plaques are targeted and subsequently eliminated, potentially uncovering the occurrence of micro-hemorrhage {{cite journal |last1=Hansen |first1=Scott B. |last2=Wang |first2=Hao |title=The shared role of cholesterol in neuronal and peripheral inflammation |journal=Pharmacology & Therapeutics |date=September 2023 |volume=249 |pages=108486 |doi=10.1016/j.pharmthera.2023.108486}}{{cite journal |last1=Hansen |first1=Scott B. |title=Cholesterol’s Function and Origin in the Alzheimer’s Disease Brain |journal=Journal of Alzheimer's Disease |date=18 July 2023 |volume=94 |issue=2 |pages=471–472 |doi=10.3233/JAD-230538}}

Secondly, an alternate perspective posits that the introduction of antibodies into the bloodstream triggers an immune-inflammatory response as part of the treatment regimen. This orchestrated immune reaction might inadvertently precipitate micro-hemorrhages.{{cite journal |last1=Antolini |first1=Laura |last2=DiFrancesco |first2=Jacopo C. |last3=Zedde |first3=Marialuisa |last4=Basso |first4=Gianpaolo |last5=Arighi |first5=Andrea |last6=Shima |first6=Atsushi |last7=Cagnin |first7=Annachiara |last8=Caulo |first8=Massimo |last9=Carare |first9=Roxana O. |last10=Charidimou |first10=Andreas |last11=Cirillo |first11=Mario |last12=Lazzaro |first12=Vincenzo Di |last13=Ferrarese |first13=Carlo |last14=Giossi |first14=Alessia |last15=Inzitari |first15=Domenico |last16=Marcon |first16=Michela |last17=Marconi |first17=Roberto |last18=Ihara |first18=Masafumi |last19=Nitrini |first19=Ricardo |last20=Orlandi |first20=Berardino |last21=Padovani |first21=Alessandro |last22=Pascarella |first22=Rosario |last23=Perini |first23=Francesco |last24=Perini |first24=Giulia |last25=Sessa |first25=Maria |last26=Scarpini |first26=Elio |last27=Tagliavini |first27=Fabrizio |last28=Valenti |first28=Raffaella |last29=Vázquez-Costa |first29=Juan Francisco |last30=Villarejo-Galende |first30=Alberto |last31=Hagiwara |first31=Yuta |last32=Ziliotto |first32=Nicole |last33=Piazza |first33=Fabrizio |title=Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy–Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study |journal=Neurology |date=2 November 2021 |volume=97 |issue=18 |pages=e1809–e1822 |doi=10.1212/WNL.0000000000012778|doi-access=free |hdl=10281/327960 |hdl-access=free }}

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Category:Anti-amyloid monoclonal antibodies

Category:Neuroimaging

Category:Magnetic resonance imaging