the neuropathology of neurodegenerative diseases

8/9/2019 The Neuropathology of Neurodegenerative Diseases

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NP of neurodegenerative diseasesNP of neurodegenerative diseases

Alzheimer’s Disease (ADPar!i"s#"’s DiseaseDeme"$ia %i$h Le%& '# ies (DL'Pi)!’s DiseasePr#*ressi+e S,-ra",)lear Pals& (PSPH,"$i"*$#"’s DiseaseAm$r#-hi) La$eral S)ler#sis (ALSPri#" E")e-hal#-a$hies (C.DHIV e")e-hali$is (AIDS eme"$ia


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Al heimer!s Disease Al heimer!s Disease

Gr#ss/ C#r$i)al a$r#-h&

0 Fr#"$al1 -arie$al a" $em-#ral l#2es

/ 3esial $em-#ral l#2e a$r#-h&0 Am&* ala1 hi--#)am-,s1 e"$#rhi"al )#r$e4


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AD" gross AD" gross


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AD gross AD gross

am&* ala

hi--#)am-,s


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AD" beta$A% amyloid pla#ues AD" beta$A% amyloid pla#ues


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Pla#ues" di&use or neuriti'Pla#ues" di&use or neuriti'

;Se"ile< -la ,es are see" %i$h 'iels)h#%s!&s$ai" a" ha+e 2ee" i+i e i"$# i=,se a""e,ri$i) s,2$&-es> 5r#m CERAD ha" 2##!


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Neuriti' pla#uesNeuriti' pla#ues

CERAD (C#"s#r$i,m $# Es$a2lish a Re*is$r& 5#r Alzheimer’sDisease )ri$eria 5#r $he "e,r#-a$h#l#*i)al ia*"#sis #5AD is 2ase #" a )li"i)al his$#r& #5 eme"$ia a" a*e?rela$e ",m2ers #5 "e,ri$i) -la ,es


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Neuro+brillary tanglesNeuro+brillary tangles

NFTs are als#e$e)$e %i$h$he'iels)h#%s!&sil+er s$ai">


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Neuro+brillary tanglesNeuro+brillary tangles

NFTs are )#m-#se #5 92rillara**re*a$es (a2#+e ma e #5-aire heli)al 9lame"$s >

The& are +er& i"s#l,2le a"remai" as ; *h#s$ $a"*les <(ri*h$1 arr#%s a5$er $he ea$h#5 $he h#s$ "e,r#">


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au a''umulation in ADau a''umulation in AD

NFTs are ma e #5 a2"#rmal a)),m,la$i#"s #5h&er-h#s-h#r&la$e $a, -r#$ei">I" $he la$e s$a*es #5 AD1 NFTs are 5re ,e"$ i" "e#)#r$i)al areasa" a))#m-a"ie 2& ",mer#,s "e,r#-il $hrea s asem#"s$ra$e %i$h $hese $a, imm,"#s$ai"s


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-raa staging-raa staging The se+eri$& #5 NFT

)ha"*es)#rrela$es %ell%i$h $he e*ree#5 )li"i)aleme"$ia>

NFTs )ha"*es aree+al,a$ea))#r i"* $# $he'raa! s$a*i"*

s&s$em(NFT


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Par inson!s DiseasePar inson!s Disease

Par!i"s#"’s Disease is )hara)$erize 2& l#ss #5-i*me"$ i" $he s,2s$a"$ia "i*ra a" l#),s)er,le,s


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Le/y -odiesLe/y -odies

Le%& 2# ies i" $he s,2s$a"$ia "i*ra are rela$i+el& eas& $#see %i$h s$a" ar H E s$ai"s a" are esse"$ial 5#r $heia*"#sis #5 Par!i"s#"’s Disease>


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Le/y -odiesLe/y -odiesLe%& 2# ies are

a2"#rmala**re*a$es #5al-ha?s&",)lei" >Imm,"#s$ai"i"*5#r al-ha?

s&",)lei" s$r#"*l& la2els2#$h Le%&'# ies a" Le%&"e,ri$es i" $he

s,2s$a"$ia "i*ra>'#$h are als#,2i ,i$i" ?-#si$i+e>


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Alpha$synu'leinopathies Alpha$synu'leinopathies

Se+eral "e,r# e*e"era$i+e iseases are)hara)$erize 2& a2"#rmal i"$ra)ell,lara**re*a$i#" #5 al-ha?s&",)lei" :

Par!i"s#"’s Disease

Deme"$ia %i$h Le%& '# iesLe%& '# & Varia"$ #5 AD3,l$i-le S&s$em A$r#-hies

OPCASNDSh&?Dra*er S&" r#me


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Dementia /ith Le/y -odiesDementia /ith Le/y -odies

Dia*"#s$i) $ermi"#l#*&:Di=,se Le%& 2# & iseaseLe%& 2# & +aria"$ #5 AD

Le%& 2# & eme"$iaSe"ile eme"$ia #5 Le%& 2# & $&-eAD %i$h i")i e"$al Le%& 2# ies

AD -l,s Par!i"s#"’s isease


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(0R *(AL L)12 -0D*)3(0R *(AL L)12 -0D*)3

i$h s$a" ar H E s$ai"1 Le%& 2# ies i" )#r$i)al"e,r#"s ma&2e i ),l$ $# a--re)ia$e>


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Le/y bodies in ADLe/y bodies in AD

Usi"* al-ha?s&",)lei" $# e$e)$Le%& 2# ies1 %e 5#," $ha$ 7J #5AD )ases ha+e Le%& 2# ies


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Pi' !s DiseasePi' !s Disease

Varia2le ",m2ers #5 Pi)! 2# ies )a" 2e see" 2& H E1'iels)h#%s!& a" $a, imm,"#s$ai"s> Pi)! )ells (2all##")ells are #5$e" -rese"$>

Ta,

PICK CELL


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Progressive 3upranu'lear Palsy Progressive 3upranu'lear Palsy

PSP $&-i)all& sh#%s se+ere e-i*me"$a$i#" #5$he s,2s$a"$ia "i*ra a" l#),s )er,le,s


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P3PP3P The m#s$ )#mm#" areas

a=e)$e i" PSP:SN1 GP1 hi--#)am-,s1

e"$#rhi"al )#r$e4 1s,2$halami) ",)lei 1e"$a$e ",)lei1 re",)lei1 -eria ,e ,)$al*ra& ma$$er1 )#lli),li1as %ell as CN III1 IV1 a" II ",)lei>

P,$ame"1 -#"$i"e ",)lei1#li+ar& ",)lei1 a")#r$e4 ma& als# sh#%*l#2#se $a"*les>


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Huntington!s DiseaseHuntington!s DiseaseN#rmal 2rai"

(le5$ )#m-are$# HD )ase(ri*h$ sh#%i"*se+ere a$r#-h&#5 )a, a$e


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Huntington!s DiseaseHuntington!s Disease

The )a, a$e sh#%s "e,r#"al l#ss a" se+ere *li#sis> L#ss#5 as-i"& (small1 ACh "e,r#"s M $ha" s-i"& (lar*e1GA'A "e,r#"s>


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Huntington!s DiseaseHuntington!s Disease

Ca, a$e a$r#-h& isassesse ,si"*$he V#"sa$$el*ra i"* s&s$em


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Amyotrophi' Lateral 3'lerosis Amyotrophi' Lateral 3'lerosis

I" )er+i)al a" l,m2ar re*i#"s1 $he a"$eri#r h#r"s ha+e",mer#,s lar*e l#%er m#$#r "e,r#"s (le5$ %hi)h arel#s$ i" ALS (ri*h$ >


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I" remai"i"* L3N1 $here ma& 2e ',"i"a 2# ies (le5$a" lar*e h&ali"e i")l,si#"s (ri*h$


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U2i ,i$i" imm,"#s$ai"s re+eal s#me L3N %i$h,2i ,i$i" s!ei"s >


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L#ss #5 "e,r#"s i" $he m#$#r )#r$e4 isa))#m-a"ie 2& *li#sis1 %hi)h is la)!i"* i" $hea a)e"$ se"s#r& )#r$e4


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Prion en'ephalopathiesPrion en'ephalopathiesPri#" -r#$ei" is a "#rmal a2," a"$ -r#$ei" i" $he 2rai">

The 5,")$i#" is ,"!"#%"> I$ has a "#rmal se)#" ar&s$r,)$,re #mi"a$e 2& al-ha?heli)al 5#rma$i#"s a" iseasil& i*es$e 2& -r#$easesA2"#rmal -ri#" -r#$ei" ($he )a,se #5 $he -ri#" iseasesis $he same -r#$ei"1 2,$ has a se)#" ar& s$r,)$,re#mi"a$e 2& 2e$a?-lea$e shee$s1 %hi)h ma!es i$ m#re-r#"e $# a**re*a$e a" resi$a"$ $# -r#$ease i*es$i#">K"#% #"e !"#%s h#% $he i"i$ial e+e"$ $ha$ )a,ses $he-r#$ei" $# )ha"*e i$’s se)#" ar& s$r,)$,re>

A2"#rmal -ri#" -r#$ei" s#meh#% ;re)r,i$s< $he "#rmal-ri#" $# $he a2"#rmal sha-e $h,s all#%i"* 5#r;-r#-a*a$i#"< a" a))#,"$i"* 5#r $ra"smissa2ili$& #5 a"a*e"$ $ha$ la)!s RNA a" DNA


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Prion en'ephalopathiesPrion en'ephalopathies

K,r, (his$#ri)alCre,$z5el $?.a!#2/ S-#ra i)

/ Tra"smi$$e/ Familial/ Ne% +aria"$ (+C.D

Gers$ma""?S$ra,ssler?S)hei"!erFa$al 5amilial i"s#m"ia


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(4D(4D S-#"*i5#rm

)ha"*es #5 2#$h)#r$i)al a" ee-*ra& ma$$er1"e,r#"al l#ss a"*li#sis )hara)$erize$he C.D 2rai">


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(4D $ prion pla#ues(4D $ prion pla#ues

I" 6BJ #5 C.D )ases ;!,r,< (-ri#" -la ,es )a"2e 5#," i" $he )ere2ell,m


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533533

GSS has ",mer#,s -ri#" -la ,es -rimaril& i" $he )ere2ell,m> There is li$$le s-#"*i5#rm )ha"*e>

There are se+eral )li"i)al a" -a$h#l#*i)al +aria"$s #5 GSS1 2,$ allare 5amilial a" ,e $# m,$a$i#"s i" $he -ri#" *e"e>


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v(4Dv(4D

+C.D has is$i")$i+e-a$h#l#*& )#"sis$i"* #5",mer#,s )#r$i)al a")ere2ellar ; #ri < -la ,es a" m# era$e s-#"*i5#rm)ha"*e>


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H*6 )N()PHAL* *3H*6 )N()PHAL* *3

HIVE is )hara)$erize 2& m,l$i",)lea$e *ia"$)ells a" -eri+as),lar a)),m,la$i#"s #5ma)r#-ha*es1 m#s$ #5 %hi)h are HIV

the neuropathology of neurodegenerative diseases

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