Tau tangles in Alzheimer's disease

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Geraldine Snow
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1 Page 1 of 5 Home Contact Us About Us Science Pipeline News Room Quiz Resources Investors Physicians Tau tangles in Alzheimer's disease Alzheim er's disease is caused by the accum ulatio n o f tau tanglesin the brain. Norm ally, tau protein is used by the brain's neurons as a kind of "scaffo lding". B ut for reasons th at are stillunclear, as people age, th e tau protein also starts to agg reg ate into filam ents inside the neuron. These tau filam ents grow out of control. T h ey fo rm tau tangles, filling u p th e n eu ro n an d ca u sing it to b u rst. N eu ro n d ea th is irreversible. Tau protein aggregates into filam ents. The filam en ts fo rm tau tangles. Braak stage 1 Braak stage is a m easure of how m any tangles th ere a re in the brain, and where they are. Braak stage 1 is the point at which tau protein starts to clum p into tau tangles. There are no external sym p tom s at th is stage, and m ig h t take an oth er 3 0 or 4 0 yea rs b efo re th ere is noticeable dem entia but fro m th is point, further decline is inevitab le. Nearly everyone willrea ch Braak stage 1 at som e age between 40 and 90 years old. A b o u t 3 0 % o f 5 0 year olds have reached Braak stage 1, and about 50% of 6 2 year o lds. A t B ra ak stag e 1, the tau tangles have begun to fo rm in the transitional entorhinal region. T h is is a "relay station " b etween th e cortex an d th e h ippocam pus, which is criticalfor m em ory.

B ut for reasons th at are stillunclear, as people age, th e tau protein also starts to agg reg ate into filam ents inside the neuron. These tau filam ents grow out of control.

2 Page 2 of 5 Braak stage 2 By Braak stage 2, tau tangles have accum ulated further and have caused som e neurons to burst apart and die.h owever, m entaltesting stillsh o ws m inim alimpairm ent. Tangles at th is levelo r wo rse are found in th e b rain s o f ab o u t 6 0 % o f over-65s. At this stag e th e tau tan g les are much m ore extensive in the transitional entorhinal region A t B ra ak stag e 2, tau tangles are causing celldea th (yellow) in (highlighted in yellow) and have th e transitional entorhinal region, a p art o f th e brain th at filters begun to killneu ro n s h ere. T h is sensory input before passing it on to th e m em o ry. Tau protein is region is a "relay station" where aggregating in the hippocampus (pink) which is crucialfor sensory input is filtered b efo re b eing memory, and in thecortex (blue) which is associated with stored in the memory. Meanwhile, in conscious thought. th e b rain's hippocampus (pink) and neo-cortex, tau protein is also beginning to aggregate b u t h as n ot yet form ed tangles. Braak stage 3 By Braak stage 3 tau tangles and neuronaldeath have likely caused som e m em ory im pairm ent, but only about 1 0 % o f patien ts at th is stage willb e d iagnosed as sufferin g fro m d em en tia. A b o u t 4 5 % o f 8 0 year olds have reached this stage. At this stage, th e tau tan g les have b eg u n to ca u se exten sive neuronal death. The m echanism for neuronal death is th at th e tau ta n g les grow out of control. T h ey fillup the

At this stag e th e tau tan g les are much m ore extensive in the transitional entorhinal region A t B ra ak stag e 2, tau tangles are causing celldea th (yellow) in (highlighted in yellow) and have

3 Page 3 of 5 neuron, causing its m em brane to burst. N euron death is irreversible. The tau protein has form ed extensive tangles in th etransitional entorhinal region. In th e hippocampus, tau p rotein has also a g g reg a ted an d b eg u n to fo rm tan g les. And in theneo-cortext, tau protein is beginning to aggregate. Tau tangles build up inside brain cells, eventually causing them to explode and die. Braak stage 4 By Braak stage 4, even though the tau tangles still occupy only a sm allportio n o f th e b rain, they have caused significant m em ory and cognitive im pairm ent. 7 0 % o f patients with th is levelo f tan g les in th eir brain willb e d iagnosed as sufferin g fro m d em en tia. By this stage, the tau tan g les have form ed extensively in the transitional entorhinal regionand the hippocampus where they have caused neuronald ea th, and they are starting to form in the neo-cortex. T h e neo-cortex is the largest part ofth e b rain, and is involved in higher functions such as sensory perception, conscious thought and language. Tau tangles have caused the death of m any neurons in p a rts o f th e brain responsible fo r memory and spatialo rien tation, the hippocampus (pink) and the transitional entorhinal region (yello w). T h ese tan g les g ro w o u t o f co n tro l inside neurons, eventually causing th em to b u rst and die. Tangles are also starting to fo rm in th e neo-cortext (blue), a p art o f th e b rain associated with conscious th ou g h t an d h igher brain functions. Braak stage: 5 A t B ra ak stag e 5, the tau tangleshave caused extensive neuronaldeath, giving rise to severe memory and cognitive im pairm ent. About 80% of patients with th is levelo f tan g les willbe diagnosed as suffering from m oderate to severe dem entia.

Tau tangles build up inside brain cells, eventually causing them to explode and die.

4 Page 4 of 5 Tangles h ave fo rm ed exten sively in thetransitional entorhinal region, th e hippocampus, and th e neocortex. Tau tangles h avefo rm ed in m an y p arts o f th e b rain: the hippocampus(pink), the transitional entorhinal region (yellow) and the neo-cortext (blue). They have caused th e death ofm a n y n eu ro n s in th ese regions, causin g severe m em o ry an d co g n itive im pairm ent. Braak stage 6 By Braak stage 6, tau tan g les have fo rm ed extensively in the transitional entorhinal region, th e hippocampus (which is criticalfor memory), and th e neo-cortex. Average Braak stage, by age The tau tangles have caused extensive neuronal death. Allp a tients with th is m any tan g les in th eir brain willbe d iagnosed as su fferin g fro m severe dem entia. They willbe com pletely unable to take ca re o f th em selves and willhave trouble recognizing fa m ily members. The horizontalaxis shows age. The verticalaxis sh o ws wh a t p ercen ta g e o f p eo p le of that age are expected to have which Braak stage. Tan: Braak stage 1 or higher Sage: Braak stage 2 or higher Red: Braak stage 3 or higher Grey: Braak stage 4 or higher MMSE and Braak stage MMSE, th e M inim en tal S tate E xam, is a popular briefquestionnaire that is used to assess cognitive im pairm ent. If th e cognitive im pairm ent is caused by tangles, th en it relates to Braak Stage as follows: Braak MMSE Symptoms M CI Mild memory loss / im pairm ent Norm alcognitive abilities MCI is frequently a p recu rso r to A D, b u t d o es n o t lead to AD in all cases

They have caused th e death ofm a n y n eu ro n s in th ese regions, causin g severe m em o ry an d co g n itive im pairm ent.

5 Page 5 of 5 Braak MMSE Symptoms Mild AD Mild memory loss / im pairm ent Slight decrease in cognitive function Mild behaviouralchanges (e.g. depression, anxiety) Moderate AD Progressive memory loss; increasingly disorganized and confused th inking Increasing behaviouralsymptoms, including agitation, paranoia etc. N eed fo r assistance in daily activities Severe AD Severe m em ory loss and dem entia Agitation, aggression, paranoia and delusions Loss ofm otor skills Patien ts o ften require hospitalization or long-term care Im ages taken from "N europathologicalstageing ofalzheimer-related changes", Braak and Braak, Acta Neuropathol (1991) 82: This website's content is Copyright TauRx Therapeutics Website Designed By Elves Lab

hospitalization or long-term care Im ages taken from "N europathologicalstageing ofalzheimer-related changes", Braak and Braak, Acta Neuropathol (1991) 82:239-259.

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